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M9490442.TXT
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1994-09-19
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Document 0442
DOCN M9490442
TI Plasma pentamidine concentrations vary between individuals with
Pneumocystis carinii pneumonia and the drug is actively secreted by the
kidney.
DT 9411
AU Lidman C; Bronner U; Gustafsson LL; Rombo L; Department of Infectious
Diseases, Karolinska Institute, Huddinge; University Hospital, Sweden.
SO J Antimicrob Chemother. 1994 Apr;33(4):803-10. Unique Identifier :
AIDSLINE MED/94334224
AB 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 i.v. 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. Clcr 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.
DE Acquired Immunodeficiency Syndrome/COMPLICATIONS Adult Human
Injections, Intravenous Kidney/*METABOLISM Male
Pentamidine/BLOOD/*PHARMACOKINETICS/THERAPEUTIC USE Pneumonia,
Pneumocystis carinii/BLOOD/DRUG THERAPY/*METABOLISM Support, Non-U.S.
Gov't Treatment Outcome JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).