Population pharmacokinetic analysis of didanosine (2',3'-dideoxyinosine) plasma concentrations obtained in phase I clinical trials in patients with AIDS or AIDS-related complex. 1992

S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Syracuse, New York 13221-4755.

Plasma didanosine concentration data from 36 patients receiving once-a-day therapy and from 33 patients receiving twice-a-day therapy were subject to population pharmacokinetic analysis with the computer program NONMEM. Once- or twice-a-day regimens of didanosine were administered intravenously (i.v.) (dose: 0.8-33 mg/kg) during the first 2 weeks of therapy, and orally (dose: 1.6-66 mg/kg) for the remaining 4 weeks of therapy. Plasma pharmacokinetics were determined after the first and last (steady-state) i.v. and oral doses. Population pharmacokinetic parameters for the combined i.v. and oral steady-state data were (mean [%CV]): systemic clearance, CL, 0.70 (5.2) L/h/kg; central compartment volume, Vc, 0.18 (32) L/kg; steady-state distribution volume, Vdss, 0.84 (6.8) L/kg; first-order absorption rate constant, Ka, 1.3 (9.5) hr-1; and bioavailable fraction, F, 0.34 (8.5). Interindividual variability (omega) was (%CV) 22.3 and 71.0 for CL and Vc, respectively. Intraindividual (residual) variability (sigma) in plasma concentrations (%CV) was 50.2. Body weight, sex, and age did not account for the variability in either CL or Vc, and the use of alternate pharmacokinetic models did not reduce the value of intraindividual variability. Population parameters for the combined i.v. and oral first-dose data were generally similar to those for the steady-state data. The parameters can be used to design dosing regimens in patients using the Bayesian feedback approach.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000386 AIDS-Related Complex A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex (ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS. ARC,Lymphadenopathy Syndrome,AIDS Related Complex,Complex, AIDS-Related,Lymphadenopathy Syndromes,Syndrome, Lymphadenopathy,Syndromes, Lymphadenopathy
D012984 Software Sequential operating programs and data which instruct the functioning of a digital computer. Computer Programs,Computer Software,Open Source Software,Software Engineering,Software Tools,Computer Applications Software,Computer Programs and Programming,Computer Software Applications,Application, Computer Software,Applications Software, Computer,Applications Softwares, Computer,Applications, Computer Software,Computer Applications Softwares,Computer Program,Computer Software Application,Engineering, Software,Open Source Softwares,Program, Computer,Programs, Computer,Software Application, Computer,Software Applications, Computer,Software Tool,Software, Computer,Software, Computer Applications,Software, Open Source,Softwares, Computer Applications,Softwares, Open Source,Source Software, Open,Source Softwares, Open,Tool, Software,Tools, Software
D016049 Didanosine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. 2',3'-Dideoxyinosine,Dideoxyinosine,ddI (Antiviral),NSC-612049,Videx,2',3' Dideoxyinosine,NSC 612049,NSC612049

Related Publications

S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
October 1993, Clinical and diagnostic virology,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
January 1990, Reviews of infectious diseases,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
May 1990, The New England journal of medicine,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
November 1991, The American journal of medicine,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
January 1990, Reviews of infectious diseases,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
January 1993, The Journal of infectious diseases,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
September 1990, Lancet (London, England),
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
June 1994, The Journal of infectious diseases,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
May 1990, The New England journal of medicine,
S M Pai, and U A Shukla, and T H Grasela, and C A Knupp, and R Dolin, and F T Valentine, and C McLaren, and H A Liebman, and R R Martin, and K A Pittman
February 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,
Copied contents to your clipboard!