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
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