Pharmacokinetics of GLQ223 in rats, monkeys, and patients with AIDS or AIDS-related complex. 1991

G Gatti, and J O Kahn, and J Lifson, and R Williams, and L Turin, and P A Volberding, and J G Gambertoglio
Division of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco 94143.

The pharmacokinetics of GLQ223 administered as a single short intravenous infusion to rats, monkeys, and patients with AIDS or AIDS-related complex (ARC) are presented. GLQ223 was given at a dose of 3,500 micrograms/kg of body weight to five Sprague-Dawley rats; a dose of 300 micrograms/kg was given to three cynomolgus monkeys; and doses of 1, 8, 16, 24, and 36 micrograms/kg were given to 10 patients with AIDS and 8 patients with ARC in an escalating dose design. Plasma clearance was 0.85 +/- 0.24 liter/h/kg in rats, 0.16 +/- 0.08 liter/h/kg in monkeys, and 0.13 +/- 0.07 liter/h/kg in patients with AIDS or ARC. The volume of distribution at steady state was 0.42 +/- 0.12, 0.21 +/- 0.20, and 0.18 +/- 0.50 liter/kg in rats, monkeys, and patients, respectively. The elimination half-life was 1.3 +/- 0.4, 3.7 +/- 1.5, and 3.2 +/- 1.0 h in rats, monkeys, and patients, respectively. The disposition of GLQ223 was not dose dependent within the dose range tested in patients with AIDS or ARC. Interspecies pharmacokinetic scaling resulted in a good linear correlation for plasma clearance and the volume of distribution at steady state plotted versus species body weight on a log-log scale, indicating the predictability of elimination and distribution of GLQ223 among species. Allometric equations derived may be useful for the prediction of doses and dosage regimens to be used in animal models.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
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
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
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

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