Effect of Posaconazole on the Pharmacokinetics of Cyclosporine

R. D. COURTNEY, P. STATKEVICH, M. LAUGHLIN, J. LIM, R. P. CLEMENT, V. K. BATRA

Author address: 

Schering-Plough Research Institute, Kenilworth, NJ.

Abstract: 

Background: Posaconazole (POZ) is a broad-spectrum triazole antifungal agent developed to treat a wide variety of invasive fungal infections. Cyclosporine (CS) is metabolized by the CYP3A4 metabolic pathway, which is inhibited by POZ. Methods: This open-label, multiple-dose study was conducted to assess the potential for a drug interaction between CS and POZ. Male and female adult heart transplant patients (n = 4) maintained on CS upon entering the study, received 200 mg POZ (QD) for 10 days. Blood samples were collected on Days 1 (CS only) and 10 (CS + POZ) for pharmacokinetic analysis. CS safety monitoring was conducted on Days 2, 3, 5, 8, 21 and 28 prior to the morning CS dose. If CS concentrations were elevated dose adjustments were made. POZ and CS concentration-time data were analyzed using model-independent methods. CS maximum plasma concentration (Cmax) and area under the curve values within a dosing interval (AUC[t]) were dose normalized (DN). Results: Three of the four patients that completed the study required adjustment of their CS dose (14.3 – 28.6% reduction). The individual steady-state CS clearance values were 16-33% lower on Day 10 vs. Day 1. The DN-Cmax and DN-AUC(t) values of CS on Day 10 in the presence and absence of POZ differed by only 4.2%. The dosage adjustments were considered low, but indicated that CS concentrations increased when co-administered with POZ. Conclusion: Concomitant administration of CS and POZ led to a 0-29% reduction of CS doses in heart transplant patients. POZ was safe and well tolerated but monitoring of patient CS concentrations for dosage adjustments is recommended when CS is co-administered with POZ.
2001

abstract No: 

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Full conference title: 

ICAAC 41st
    • ICAAC 41st