A 57-year-old male renal allograft recipient in 2003 was prescribed prednisolone, MMF (1,500 mg daily) and losartan, therapeutic drug monitoring of MPA was performed twice in 2007, on both occasions, the patient was in steady state with respect to MPA pharmacokinetics and the biochemistry was normal. The MPA AUC0-12corr was 42.9 mg.h/L in April and 54.3 mg.h/L in October 2007.
The patient was from a neighbouring country and returned home. Whilst there, in early December 2007, he was diagnosed with pulmonary tuberculosis and started on anti-tubercular therapy which consisted of rifampicin, isoniazid, ethambutol, pyrazinamide and pyridoxine. Two weeks later, the patient presented to our transplant unit with mild elevation of creatinine compared to the previous visit (2.0 mg% versus 1.7 mg%). According to the protocol for the management of tuberculosis in transplant patients in our transplant unit rifampicin was discontinued and ofloxacin was started. Mycophenolate was continued at the same dose. One week after rifampicin was discontinued MPA was monitored and the MPA-AUC0-12corr was 13.9 mg.h/L. This is a 74.4% reduction in MPA-AUC0-12corr compared to the previous measurement (13.9 vs 54.3 mg.h/L in October).
Three weeks after discontinuation of rifampicin the MPA-AUC0-12corr was again measured and had increased to 35.3 mg.h/L. This is a 2.5 fold increase in the MPA-AUC0-12corr (13.9 to 35.3 mg.h/L) from two weeks earlier however, it is only 65% of the MPA-AUC0-12corr prior to rifampicin. The serum creatinine had improved to 1.7 mg%. The patient was unable to stay longer and returned home.
In July 2008 when the patient re-visited the transplant unit, MPA-AUC0-12corr was again measured and 64.1 mg.h/L. Serum albumin was within the acceptable range (3.4 to 4.7 gm/dl) throughout the period of MPA monitoring. Figure 1 shows the time course of rifampicin treatment and TDM results.