Pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS and related disorders.
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 microM (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.
Klecker
R W
RW
Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland.
Collins
J M
JM
Yarchoan
R C
RC
Thomas
R
R
McAtee
N
N
Broder
S
S
Myers
C E
CE
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism*; D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D016047:Zalcitabine; D015215:Zidovudine / Q000493:pharmacokinetics
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D015215:Zidovudine; D016047:Zalcitabine