Pharmacokinetics of 2‘,3’‐Dideoxycytidine in Patients with AIDS and Related Disorders

Journal of Clinical Pharmacology - Tập 28 Số 9 - Trang 837-842 - 1988
Raymond W. Klecker1, Jerry M. Collins1, Robert Yarchoan1, Rose V. Thomas1, Nanette McAtee1, Samuel Broder1, Charles E. Myers1
1Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland

Tóm tắt

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/m2 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.

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Tài liệu tham khảo

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Thông tin xuất bản

Journal of Clinical Pharmacology

Tập 28 Số 9

837-842

Thông tin tác giả