1 . this bioequivalence study demonstrates that the pharmacokinetic properties of gabapentin 500  mg and zolpidem tartrate 10  mg are unaffected when both treatments are taken simultaneously , compared with each drug taken alone , in healthy participants.2 .
both treatments were well tolerated when taken alone and in combination , in a population of healthy participants .
gabapentin was first developed to treat seizure disorders and neuropathic pain , and is now being investigated as a potential sleep aid for occasional disturbed sleep .
studies suggest that low - dose gabapentin ( 250  mg [ 1 , 2 ] and 500  mg ) can improve objective and subjective measures of sleep in adults using a model of occasional disturbed sleep [ 1 , 2 ] .
the exact mechanism by which gabapentin improves sleep is unknown , but is likely related to its well - characterized binding affinity to the 2 subunit of voltage - activated calcium channels , and subsequent modulatory effects on neurotransmitter release [ 3 , 4 ] .
the pharmacokinetic profile of gabapentin as an immediate - release formulation has been well defined across the therapeutic dose range ( 3001,800  mg / day , with a recommended dose of 9001,800  mg / day for approved indications ) .
for example , after single - dose oral administration ( 300 or 600  mg ) [ 57 ] , gabapentin reaches peak plasma concentration ( cmax ) in 23  h [ time to reach cmax ( tmax ) ] [ 5 , 8 ] , and with multiple dosing , achieves steady state within 2448  h .
plasma concentrations of gabapentin do not increase proportionally with increasing doses owing to absorption in only a limited segment of the small intestine .
gabapentin is eliminated unchanged through the kidney , with a terminal half - life ( t ) of 57  h .
gabapentin is largely unaffected by alteration in hepatic function or cytochrome p450 ( cyp450 ) activity [ 6 , 9 ] , and there are few known drug  drug interactions , including no interaction observed with other antiepileptic drugs ( lamotrigine , vigabatrin or oxcarbazepine )   or with a contraceptive regimen of norethindrone acetate and ethinyl estradiol .
the most common adverse events ( aes ) observed following treatment with gabapentin ( 9001,800  mg / day ) ( not seen at an equivalent frequency among placebo - treated patients ) were dizziness , somnolence and peripheral edema in adults with post - herpetic neuralgia , and somnolence , dizziness , ataxia , fatigue and nystagmus in adults with partial seizures with and without secondary generalization .
gabapentin s overall pharmacokinetic and pharmacodynamic profile makes for a predictable and well - tolerated drug .
there is potential for individuals with sleep disturbances to self - medicate with multiple sleep products .
zolpidem , an imidazopyridine agent , is widely prescribed for the short - term management of insomnia .
it is absorbed rapidly , with bioavailability of 70  % , and reaches cmax in < 1  h .
in addition , zolpidem is rapidly metabolized before being eliminated primarily in bile , urine and feces [ 15 , 16 ] . because metabolism occurs via successive cyp450 enzymes
, zolpidem has a high potential for drug  drug interactions with agents that inhibit or induce cyp450 enzymes .
although gabapentin is not metabolized via the cyp450 pathway , there is potential for co - administration with gabapentin , and therefore , any potential effects of zolpidem on the pharmacokinetic properties of gabapentin , and vice versa , warrant investigation .
drug interaction of gabapentin with zolpidem in healthy participants , when administered individually and in combination .
participants were randomized in an open - label , three - period crossover design to single - dose gabapentin ( 500  mg ) , zolpidem tartrate ( 10  mg ) , and the combination ( gabapentin 500  mg  +  zolpidem tartrate 10  mg ) , between november 5 and 21 , 2001 .
the study was conducted in compliance with the declaration of helsinki and the international conference on harmonisation good clinical practice guidelines .
protocol , consent documents and protocol amendments were all approved by the relevant institutional review board at participating centers .
healthy men and women ( of non - child - bearing potential or those using an acceptable contraceptive ) aged 18  years and weighing 50100  kg ( 110220  lbs ) were recruited .
standard exclusion criteria were imposed , including , but not limited to , participants with a known sensitivity to either drug ; a positive pregnancy test on screening ; a history of drug or alcohol abuse ; or on physical examination , any clinically significant disease or abnormality that was deemed likely to affect the properties of either drug under investigation .
venous blood ( 210  ml per participant ) was collected in heparinized collection tubes pre - dose ( 0 
h ) and at 0.5 , 1 , 1.5 , 2 , 3 , 4 , 6 , 8 , 10 , 12 , 18 , 24 and 36  h post - dose .
samples were centrifuged and the plasma stored in labeled , screw - capped , polypropylene tubes at 20 c within 1  h of collection .
gabapentin plasma concentrations were determined by validated liquid chromatography tandem mass spectrometry methods using 1-(amino - methyl)-cycloheptaneacetic acid ( pd0403609 - 0000 ) as an internal standard ( bioassay laboratories , houston , tx , usa ) .
the analytical range for detection of gabapentin was 0.02510.0  g / ml , with precision [ % coefficient of variation ( cv ) ] 15.5  % and accuracy [ % relative error ( re ) ] of 0.26.7  % .
zolpidem plasma concentrations were determined by a validated high - throughput liquid chromatography ( hplc ) with fluorescence detection , using trazodone as an internal standard ( covance laboratories , inc . ,
the analytical range of detection for zolpidem was 1.00400  ng / ml , with precision ( % cv ) 14  % and accuracy ( % re ) of 2.05.0  % .
the cmax and tmax were observed directly from the plasma concentration  time profile of each participant .
time curve from time zero to time of last quantifiable concentration ( tlqc ) ( auc0tlqc ) was evaluated using the linear trapezoidal method .
the t was calculated using the terminal rate constant determined from the terminal log - linear phase of the concentration 
data were reviewed and accepted by quality - control specialists before being used for pharmacokinetic analyses .
safety evaluations were conducted throughout the study and included monitoring of aes , vital signs , 12-lead electrocardiograms , and physical examination including blood pressure , respiratory , and pulse rate .
laboratory tests were conducted at screening only . a sample size of 36 participants completing the study was estimated on the basis of estimates of intra - subject cv for zolpidem 10  mg , which is larger than that for gabapentin [ 18 , 19 ] . the sample size provided at least 80  % power to demonstrate bioequivalence with respect to auc0 and cmax , assuming a cv of 33  % and no underlying difference between the combination and each drug administered alone .
log - transformed auc0 and cmax were analyzed using analysis of variance ( anova ) with treatment sequence , period and treatment as fixed effects and subject - within - sequence as a random effect .
results from the anova were used to calculate 90  % confidence intervals ( cis ) for the ratios ( test / reference ) of least - squares mean treatment values , where administration of gabapentin and zolpidem together was the test treatment and administration of gabapentin alone and zolpidem alone were the reference treatments .
lack of an interaction was concluded if the estimated 90  % cis for the ratios ( test / reference ) of adjusted means for both auc0 and cmax fell within the 80125  % accepted range for bioequivalence .
participants were randomized in an open - label , three - period crossover design to single - dose gabapentin ( 500  mg ) , zolpidem tartrate ( 10  mg ) , and the combination ( gabapentin 500  mg  +  zolpidem tartrate 10  mg ) , between november 5 and 21 , 2001 .
the study was conducted in compliance with the declaration of helsinki and the international conference on harmonisation good clinical practice guidelines .
protocol , consent documents and protocol amendments were all approved by the relevant institutional review board at participating centers .
all participants provided written , informed consent prior to randomization . healthy men and women ( of non - child - bearing potential or those using an acceptable contraceptive )
aged 18  years and weighing 50100  kg ( 110220  lbs ) were recruited .
standard exclusion criteria were imposed , including , but not limited to , participants with a known sensitivity to either drug ; a positive pregnancy test on screening ; a history of drug or alcohol abuse ; or on physical examination , any clinically significant disease or abnormality that was deemed likely to affect the properties of either drug under investigation .
venous blood ( 210  ml per participant ) was collected in heparinized collection tubes pre - dose ( 0  h ) and at 0.5 , 1 , 1.5 , 2 , 3 , 4 , 6 , 8 , 10 , 12 , 18 , 24 and 36  h post - dose .
samples were centrifuged and the plasma stored in labeled , screw - capped , polypropylene tubes at 20 c within 1  h of collection .
gabapentin plasma concentrations were determined by validated liquid chromatography tandem mass spectrometry methods using 1-(amino - methyl)-cycloheptaneacetic acid ( pd0403609 - 0000 ) as an internal standard ( bioassay laboratories , houston , tx , usa ) .
the analytical range for detection of gabapentin was 0.02510.0  g / ml , with precision [ % coefficient of variation ( cv ) ] 15.5  % and accuracy [ % relative error ( re ) ] of 0.26.7  % .
zolpidem plasma concentrations were determined by a validated high - throughput liquid chromatography ( hplc ) with fluorescence detection , using trazodone as an internal standard ( covance laboratories , inc . , madison , wi , usa ) .
the analytical range of detection for zolpidem was 1.00400  ng / ml , with precision ( % cv ) 14  % and accuracy ( % re ) of 2.05.0  % .
non - compartmental methods were employed to estimate pharmacokinetic parameters . the cmax and tmax were observed directly from the plasma concentration  time profile of each participant .
time curve from time zero to time of last quantifiable concentration ( tlqc ) ( auc0tlqc ) was evaluated using the linear trapezoidal method .
the t was calculated using the terminal rate constant determined from the terminal log - linear phase of the concentration 
data were reviewed and accepted by quality - control specialists before being used for pharmacokinetic analyses .
safety evaluations were conducted throughout the study and included monitoring of aes , vital signs , 12-lead electrocardiograms , and physical examination including blood pressure , respiratory , and pulse rate .
a sample size of 36 participants completing the study was estimated on the basis of estimates of intra - subject cv for zolpidem 10  mg , which is larger than that for gabapentin [ 18 , 19 ] . the sample size provided at least 80  % power to demonstrate bioequivalence with respect to auc0 and cmax , assuming a cv of 33  % and no underlying difference between the combination and each drug administered alone .
log - transformed auc0 and cmax were analyzed using analysis of variance ( anova ) with treatment sequence , period and treatment as fixed effects and subject - within - sequence as a random effect .
results from the anova were used to calculate 90  % confidence intervals ( cis ) for the ratios ( test / reference ) of least - squares mean treatment values , where administration of gabapentin and zolpidem together was the test treatment and administration of gabapentin alone and zolpidem alone were the reference treatments .
lack of an interaction was concluded if the estimated 90  % cis for the ratios ( test / reference ) of adjusted means for both auc0 and cmax fell within the 80125  % accepted range for bioequivalence .
three participants were withdrawn because of positive urine drug screens ( one prior to the second treatment period and two prior to the third treatment period ) , and one participant did not return for the third treatment period . because of these withdrawals , 39 participants received gabapentin ( 500  mg ) , 38 received zolpidem tartrate ( 10  mg ) , and 38 received the combination and were included in the pharmacokinetic analyses ( table  1 ) . during the study , no participant took or received concomitant therapy that was judged to have the potential to affect pharmacokinetic parameters.table  1demographic characteristics of randomized participants at baseline ( n  =  40)characteristicnumber ( % ) or mean    standard deviation 
 male : female19:21age , years34.1    8.1  range1845race  white24 ( 60 )  black , non - hispanic7 ( 18 )  other9 ( 23)weight ( kg)68.3    9.7  range51.492.7body mass index ( kg / m)25.4    2.7  range20.732.1 
 unless otherwise specified demographic characteristics of randomized participants at baseline ( n  =  40 ) 
 unless otherwise specified the mean plasma concentration 
time profiles for gabapentin and zolpidem following administration alone or in combination are shown in figs .  1 and 2 , respectively .
for gabapentin  +  zolpidem combination versus gabapentin alone , the mean pharmacokinetic parameters were cmax 4.61 versus 4.72  g / ml , tmax 4.63 versus 3.64  h and auc0 53.4 versus 51.0  g  h / ml ( table  2 ) .
the 90  % cis for the treatment ratio of cmax ( 92.0102.0 ) and auc0 ( 99.0109.0 ) for the combination versus gabapentin alone were within the 80125  % range accepted for bioequivalence ( table  2 ) .
for the combination versus zolpidem alone , the mean pharmacokinetic parameters were cmax 154.0 versus 138.0  ng / ml , tmax 1.45 versus 1.84  h and auc0 912.0 versus 854.0  ng  h / ml ( table 3 ) .
the 90  % cis for the treatment ratio of cmax ( 104.0118.0 ) and auc0 ( 98.1112.0 ) for the combination versus zolpidem alone were within the 80125  % range accepted for bioequivalence ( table 3 ) .
the t of gabapentin or zolpidem was also similar when administered alone versus in combination , and averaged ~5.5  h for gabapentin and 3.4  h for zolpidem.fig . 
time profiles following administration of zolpidem tartrate alone and with gabapentintable  2summary of pharmacokinetic parameters for gabapentin co - administered with zolpidem tartrate ( test ) and for gabapentin alone
( reference)parameter ( units)gabapentin  +  zolpidem ( test ) [ mean ( sd)]gabapentin ( reference ) [ mean ( sd)]ratio ( % ) 
 90  % confidence interval 
 lowerupper 
 n 
 3838 
 c 
 max ( g / ml)4.61 ( 1.11)4.72 ( 1.18)97.092.0102.0auc0tlqc ( g  h / ml)52.5 ( 12.6)50.2 ( 12.1)104.098.8109.0auc0 ( g  h / ml)53.4 ( 12.9)51.0 ( 12.4)104.099.0109.0 
 t 
 max ( h)4.63 ( 1.95)3.64 ( 1.17) 
 t 
  ( h)5.47 ( 1.06)5.49 ( 0.86) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed datatable  3summary of pharmacokinetic parameters for zolpidem co - administered with gabapentin ( test ) and for zolpidem tartrate alone
( reference)parameter ( units)zolpidem  +  gabapentin ( test ) [ mean ( sd)]zolpidem ( reference ) [ mean ( sd)]ratio ( % ) 
 90  % confidence interval 
 lowerupper 
 n 
 3837 
 c 
 max ( ng / ml)154 ( 49.9)138 ( 43.9)111.0104.0118.0auc0tlqc ( ng  h / ml)898 ( 381)842 ( 338)105.098.0112.0auc0 ( ng  h / ml)912 ( 386)854 ( 341)105.098.1112.0 
 t 
 max ( h)1.45 ( 0.94)1.84 ( 1.23) 
 t 
  ( h)3.47 ( 1.17)3.44 ( 1.21) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data mean gabapentin plasma concentration 
time profiles following administration of gabapentin alone and with zolpidem tartrate mean zolpidem plasma concentration  time profiles following administration of zolpidem tartrate alone and with gabapentin summary of pharmacokinetic parameters for gabapentin co - administered with zolpidem tartrate ( test ) and for gabapentin alone ( reference ) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data summary of pharmacokinetic parameters for zolpidem co - administered with gabapentin ( test ) and for zolpidem tartrate alone ( reference ) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data co - administration of gabapentin and zolpidem was well tolerated .
five participants reported seven treatment - emergent aes ; all were mild in severity ( table  4 ) .
no deaths , serious or severe aes , or discontinuations due to aes were reported .
in addition , no clinically significant changes in vital signs were recorded pre- versus post-study.table  4summary and frequency of aes for participants treated with gabapentin alone , zolpidem alone , or gabapentin  +  zolpidemgabapentinzolpidemgabapentin  +  zolpidemevaluable participants393838  participants [ n ( % ) ] reporting aes1 ( 2.6)3 ( 7.9)1 ( 2.6 )  participants [ n ( % ) ] withdrawing due to aes0 ( 0)0 ( 0)0 ( 0 )  participants [ n ( % ) ] with treatment - related aes 
 1 ( 2.6)3 ( 7.9)1 ( 2.6)number of aes142number of serious aes000number of aes by intensity  mild142  moderate / severe000participants ( n ) reporting ae ( by type )  dizziness011  headache110  vomiting010 
 ae adverse event 
 considered by the investigator to be related to treatment summary and frequency of aes for participants treated with gabapentin alone , zolpidem alone , or gabapentin  +  zolpidem 
 considered by the investigator to be related to treatment
three participants were withdrawn because of positive urine drug screens ( one prior to the second treatment period and two prior to the third treatment period ) , and one participant did not return for the third treatment period . because of these withdrawals , 39 participants received gabapentin ( 500  mg ) , 38 received zolpidem tartrate ( 10  mg ) , and 38 received the combination and were included in the pharmacokinetic analyses ( table  1 ) . during the study , no participant took or received concomitant therapy that was judged to have the potential to affect pharmacokinetic parameters.table  1demographic characteristics of randomized participants at baseline ( n  =  40)characteristicnumber ( % ) or mean    standard deviation 
 male : female19:21age , years34.1    8.1  range1845race  white24 ( 60 )  black , non - hispanic7 ( 18 )  other9 ( 23)weight ( kg)68.3    9.7  range51.492.7body mass index ( kg / m)25.4    2.7  range20.732.1 
 unless otherwise specified demographic characteristics of randomized participants at baseline ( n  =  40 ) 
 unless otherwise specified
the mean plasma concentration  time profiles for gabapentin and zolpidem following administration alone or in combination are shown in figs .  1 and 2 , respectively . for gabapentin 
+  zolpidem combination versus gabapentin alone , the mean pharmacokinetic parameters were cmax 4.61 versus 4.72  g / ml , tmax 4.63 versus 3.64  h and auc0 53.4 versus 51.0  g  h / ml ( table  2 ) .
the 90  % cis for the treatment ratio of cmax ( 92.0102.0 ) and auc0 ( 99.0109.0 ) for the combination versus gabapentin alone were within the 80125  % range accepted for bioequivalence ( table  2 ) .
for the combination versus zolpidem alone , the mean pharmacokinetic parameters were cmax 154.0 versus 138.0  ng / ml , tmax 1.45 versus 1.84  h and auc0 912.0 versus 854.0  ng  h / ml ( table 3 ) .
the 90  % cis for the treatment ratio of cmax ( 104.0118.0 ) and auc0 ( 98.1112.0 ) for the combination versus zolpidem alone were within the 80125  % range accepted for bioequivalence ( table 3 ) .
the t of gabapentin or zolpidem was also similar when administered alone versus in combination , and averaged ~5.5  h for gabapentin and 3.4  h for zolpidem.fig . 
time profiles following administration of zolpidem tartrate alone and with gabapentintable  2summary of pharmacokinetic parameters for gabapentin co - administered with zolpidem tartrate ( test ) and for gabapentin alone ( reference)parameter
( units)gabapentin  +  zolpidem ( test ) [ mean ( sd)]gabapentin ( reference ) [ mean ( sd)]ratio ( % ) 
 90  % confidence interval 
 lowerupper 
 n 
 3838 
 c 
 max ( g / ml)4.61 ( 1.11)4.72 ( 1.18)97.092.0102.0auc0tlqc ( g  h / ml)52.5 ( 12.6)50.2 ( 12.1)104.098.8109.0auc0 ( g  h / ml)53.4 ( 12.9)51.0 ( 12.4)104.099.0109.0 
 t 
 max ( h)4.63 ( 1.95)3.64 ( 1.17) 
 t 
  ( h)5.47 ( 1.06)5.49 ( 0.86) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed datatable  3summary of pharmacokinetic parameters for zolpidem co - administered with gabapentin ( test ) and for zolpidem tartrate alone ( reference)parameter
( units)zolpidem  +  gabapentin ( test ) [ mean ( sd)]zolpidem ( reference ) [ mean ( sd)]ratio ( % ) 
 90  % confidence interval 
 lowerupper 
 n 
 3837 
 c 
 max ( ng / ml)154 ( 49.9)138 ( 43.9)111.0104.0118.0auc0tlqc ( ng  h / ml)898 ( 381)842 ( 338)105.098.0112.0auc0 ( ng  h / ml)912 ( 386)854 ( 341)105.098.1112.0 
 t 
 max ( h)1.45 ( 0.94)1.84 ( 1.23) 
 t 
  ( h)3.47 ( 1.17)3.44 ( 1.21) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data mean gabapentin plasma concentration 
time profiles following administration of gabapentin alone and with zolpidem tartrate mean zolpidem plasma concentration  time profiles following administration of zolpidem tartrate alone and with gabapentin summary of pharmacokinetic parameters for gabapentin co - administered with zolpidem tartrate ( test ) and for gabapentin alone ( reference ) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data summary of pharmacokinetic parameters for zolpidem co - administered with gabapentin ( test ) and for zolpidem tartrate alone ( reference ) 
 auc area under the concentration  time curve , c 
 max peak plasma concentration , sd standard deviation , t 
  terminal half - life , tlqc time of last quantifiable concentration , t 
 max time to peak plasma concentration 
 ratio of mean values , and the confidence interval for the ratio expressed as percentage , based on the model fitted to natural log - transformed data
five participants reported seven treatment - emergent aes ; all were mild in severity ( table  4 ) .
no deaths , serious or severe aes , or discontinuations due to aes were reported .
in addition , no clinically significant changes in vital signs were recorded pre- versus post-study.table  4summary and frequency of aes for participants treated with gabapentin alone , zolpidem alone , or gabapentin  +  zolpidemgabapentinzolpidemgabapentin  +  zolpidemevaluable participants393838  participants [ n ( % ) ] reporting aes1 ( 2.6)3 ( 7.9)1 ( 2.6 )  participants [ n ( % ) ] withdrawing due to aes0 ( 0)0 ( 0)0 ( 0 )  participants [ n ( % ) ] with treatment - related aes 
 1 ( 2.6)3 ( 7.9)1 ( 2.6)number of aes142number of serious aes000number of aes by intensity  mild142  moderate / severe000participants ( n ) reporting ae ( by type )  dizziness011  headache110  vomiting010 
 ae adverse event 
 considered by the investigator to be related to treatment summary and frequency of aes for participants treated with gabapentin alone , zolpidem alone , or gabapentin  +  zolpidem 
 considered by the investigator to be related to treatment
gabapentin is being investigated as a potential sleep aid for occasional disturbed sleep on the basis of clinical evidence from healthy volunteers and patients with insomnia [ 1 , 2 , 2023 ] .
the present study demonstrated that the pharmacokinetics of gabapentin ( 500  mg ) and a commonly prescribed prescription sleep aid , zolpidem tartrate ( 10  mg ) , were unaffected when both drugs were administered simultaneously , compared with each drug taken alone . in addition , both drugs at the doses stated were well tolerated when taken alone or in combination in this group of healthy individuals .
zolpidem is widely prescribed in clinical practice for short - term management of insomnia , and is generally safe and well tolerated [ 24 , 25 ] .
although not recommended , the nature of occasional sleep disturbance may result in individuals self - medicating with multiple sleep aids to improve sleep [ 26 , 27 ] . of concern
, many prescription sleep aids are associated with significant residual next - day effects due to long half - lives , which could be further prolonged with a change to the pharmacokinetic elimination parameters .
our data demonstrate that administration of gabapentin with zolpidem was bioequivalent to administration of gabapentin alone , as the 90  % cis for cmax ( rate of absorption ) and auc0 ( extent of absorption ) comparing single drug administration versus each drug administered in combination were within the 80125  % range accepted for bioequivalence .
in addition , administration of gabapentin or zolpidem alone or in combination did not change the t for either drug .
therefore , no prolonging of next - day effects of zolpidem would be expected , although pharmacodynamic studies would be needed to confirm this assumption .
overall , our study found no new safety signals for single - dose use of these two drugs when co - administered .
our observations also support what is known about the pharmacokinetic properties of both drugs , as drug  drug interactions would not be expected between gabapentin and zolpidem .
for example , zolpidem is metabolized via cyp3a4 , and acts as a mild mechanism - based inactivator of human cyp3a in vitro [ 29 , 30 ] .
in contrast , gabapentin is non - metabolized and is eliminated renally primarily as unchanged drug , showing plasma clearance that is proportional to creatinine clearance .
it should be noted that the present study was conducted in a small study population of healthy individuals , using only a single dose , and should be interpreted in light of this .
in addition , our observations might not be extrapolated to elderly participants , or those with reduced renal function , as data have shown that age - related changes in renal function can alter the pharmacokinetics of gabapentin [ 31 , 32 ] .
the pharmacokinetic properties of gabapentin 500  mg and zolpidem tartrate 10  mg are unaffected when both treatments are taken simultaneously , compared with each treatment taken alone .
all treatments were well tolerated when taken alone or in combination in this study population .
furey are full - time employees of , and hold stock options in , pfizer inc .
 objectivegabapentin is being investigated as a potential treatment for occasional disturbed sleep . 
 this study assessed the pharmacokinetics and tolerability of gabapentin 500  mg and the commonly prescribed sedative / hypnotic zolpidem tartrate 10  mg , administered separately and in combination.methodsforty healthy participants ( 19 male , 21 female ) were randomized into this three - period crossover study [ mean ( range ) age 34.1 ( 1845 )  years , weight 68.3 ( 51.492.7 )  kg ; 60  % white ] . 
 participants were dosed with gabapentin alone ( n  =  39 ) , zolpidem tartrate alone ( n  =  38 ) , and the combination ( gabapentin  +  zolpidem ) ( n  =  38 ) over three treatment periods , which were separated by 7  days . 
 blood samples were collected pre - dose and 0.5 , 1 , 1.5 , 2 , 3 , 4 , 6 , 8 , 10 , 12 , 18 , 24 and 36  h post - dose . 
 plasma concentrations of each drug were assayed using validated methods . 
 pharmacokinetic parameters were estimated from plasma concentration  time data using standard non - compartmental methods.resultsfor gabapentin  +  zolpidem combination versus gabapentin alone , mean pharmacokinetic parameters were peak plasma concentration ( cmax ) 4.61 versus 4.72  g / ml , time to cmax ( tmax ) 4.63 versus 3.64  h and the area under plasma concentration  time curve extrapolated to infinity ( auc0 ) 53.4 versus 51.0  g  h / ml . for the combination versus 
 zolpidem alone , mean pharmacokinetic parameters were cmax 154 versus 138  ng / ml , tmax 1.45 versus 1.84  h and auc0 912 versus 854  ng  h / ml . the 90  % confidence intervals for cmax ( rate of absorption ) and auc0 ( extent of absorption ) comparing the combination versus single drug administration fell within the 80125  % range accepted for bioequivalence . 
 all treatments were well tolerated.conclusionthe pharmacokinetics of gabapentin 500  mg and zolpidem tartrate 10  mg are unaffected when both drugs are taken simultaneously , compared with each drug taken alone . 
Key Points
Introduction
Methods
Study Design
Participants
Analysis of Plasma Samples
Pharmacokinetic Parameters
Safety and Tolerability
Statistical Analyses
Results
Study Population
Pharmacokinetic Analyses
Safety and Tolerability
Discussion
Conclusions
Disclosures