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Pharmacokinetics of 2‘,3’‐Dideoxycytidine in Patients with AIDS and Related Disorders
Author(s) -
Klecker Raymond W.,
Collins Jerry M.,
Yarchoan Robert C.,
Thomas Rose,
McAtee Nanette,
Broder Samuel,
Myers Charles E.
Publication year - 1988
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1988.tb03225.x
Subject(s) - pharmacokinetics , bioavailability , volume of distribution , urine , pharmacology , chemistry , dosing , high performance liquid chromatography , half life , distribution volume , distribution (mathematics) , bioequivalence , clearance , oral administration , chromatography , medicine , urology , biochemistry , mathematical analysis , mathematics
The clinical pharmacokinetics of 2′,3′‐dideoxycytidine (DDC) were determined after oral and intravenous administration in ten patients with AIDS or AIDS‐related complex. A high performance liquid chromatography (HPLC) analysis procedure using cation exchange extraction columns was used to measure DDC levels as low as 0.1 μM (21 ng/mL) in plasma and urine. The kinetics of DDC were linear over the dose range of 0.03 to 0.5 mg/kg. Total body clearance was 227 mL/min/m 2 and did not change after 6 to 14 days of dosing. The volume of distribution at steady state was 0.54 L/kg. Plasma half‐life was 1.2 hours, and bioavailability was 88%. Most (75%) of the parent drug was found unchanged in the urine. As a result, renal function could play a role in dose adjustment of DDC. Comparison is made between the kinetics of DDC and 3′‐azido‐2′,3′‐dideoxythymidine (AZT). Similarities are noted in half‐life and bioavailability. However, differences are observed for total body clearance, cerebrospinal fluid penetration, volume of distribution, metabolism, and recovery in urine.