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Journal of Antimicrobial Chemotherapy (1994) 33, 803-810
© 1994 The British Society for Antimicrobial Chemotherapy

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Plasma pentamidine concentrations vary between individuals with Pneumocystis carinii pneumonia and the drug is actively secreted by the kidney

C. Lidmana, U. Bronnera,b, L. L. Gustafssonb and L. Romboa

aDepartment of Infectious Diseases, Karolinska Institute, Huddinge University Hospital Huddinge, Sweden bDepartment of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital Huddinge, Sweden

Received 18 January 1993; accepted 31 August 1993

The multiple-dose pharmacokinetics of pentamidine were studied in six AIDS patients with acute Pneumocystis carinii pneumonia given infusions of pentamidine isethionate 3•7–4 mg/kg/day iv. Plasma and urine concentrations of pentamidine of repeated samples taken on days 1, 4 and 7 of treatment were assayed by HPLC. Creatinine clearance Clcr was also determined. On day 7, the area under the plasma concentration versus time curve (AUC) varied fourfold (3263 to 12776 nmol.h/L) between individuals. It was lowest in a patient receiving concomitant treatment with carbamazepine, suggesting that this drug may induce the metabolism of pentamidine. On day 7, a mean of 12% of the dose was excreted unchanged in the urine. Clr was decreased significantly on day 7 compared with day 1 (mean decrease 31%, range 11–63%). Renal clearance of pentamidine (Clr) decreased over time but always exceeded the Clcr indicating tubular secretion. The decrease of Clr may be explained by capacity-limited secretion and/or a tubulotoxic effect of the drug. The variation of the AUC values is consistent with interindividual differences in rates of metabolism, which supports individual dosing strategies for pentamidine.


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