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Plasma pentamidine concentrations vary between individuals with Pneumocystis carinii pneumonia and the drug is actively secreted by the kidney
Ist Teil von
Journal of antimicrobial chemotherapy, 1994-04, Vol.33 (4), p.803-810
Ort / Verlag
Oxford: Oxford University Press
Erscheinungsjahr
1994
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.