Pharmacokinetics of the drug pyrimethamine in study participants.
toxicity, epilepsy
EPILEPSY
(We found no clear outliers in the data on pyrimethamine and VPA plasma exposure for the seven PLWH who had treatment adjustments for toxic effects (table S6). Of those seven, the ones in the pyrimethamine-containing arms had pyrimethamine plasma levels at 6 hours after the first dose that were at or below the median plasma exposure found in the pyrimethamine monotherapy arm at that time points. All participants where pyrimethamine was stopped had clearly lower plasma levels at day 14 with the notable exception of LUNA-21 (2.52 mg/liter) who stopped treatment at day10, later than the others who interrupted pyrimethamine (table S6). In the same line, three of the five PLWH, who had their therapy adjusted for toxicity while receiving VPA, had plasma levels at day 7 exceeding the therapeutic window defined for treating epilepsy (up to 100 mg/liter) compared to three of nine who continued VPA (table S6). This provides some evidence that VPA plasma exposure related to clinical toxicity, comparable to the use of therapeutic drug monitoring of VPA for other conditions (