Comparative pharmacokinetics and interspecies scaling of amphotericin B in several mammalian species. 1997

A Hutchaleelaha, and H H Chow, and M Mayersohn
Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson 85721, USA.

This study employed several interspecies scaling methods, to evaluate the applicability of extrapolating to man, pharmacokinetic information obtained from animals for amphotericin B, an anti-fungal drug. Pharmacokinetic parameters from four animal species (mouse, rat, monkey and dog) and man were obtained from the literature or from analysis of data reported in the literature. The allometric relationships (obtained from four animal species) as a function of species body weight (W; kg) for systemic clearance per maximum life span potential (CLS/MLP), steady-state volume of distribution (VSS), apparent volume of distribution (V beta) and volume of the central compartment (VC) were: 5691W1.096; 2.46W0.839; 3.08W0.948 and 1.07W0.965, respectively. The allometric relationships for half-life (h) and mean residence time (h) did not scale well with body weight. The prediction of pharmacokinetic parameters in man from the allometric equations do not always agree with those reported in the literature which are based upon a limited number of studies with few human subjects. The plasma concentration-time profiles from these animals were adjusted by normalizing the concentration with dose/W0.948, and re-plotted on different pharmacokinetic time scales. The syndesichrons plot produced an almost superimposable profile of adjusted concentrations as a function of adjusted time among the four species.

UI MeSH Term Description Entries
D008433 Mathematics The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Mathematic
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
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
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000666 Amphotericin B Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. Amphocil,Amphotericin,Amphotericin B Cholesterol Dispersion,Amphotericin B Colloidal Dispersion,Fungizone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000882 Haplorhini A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes). Anthropoidea,Monkeys,Anthropoids,Monkey
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial

Related Publications

A Hutchaleelaha, and H H Chow, and M Mayersohn
March 1990, Journal of pharmacobio-dynamics,
A Hutchaleelaha, and H H Chow, and M Mayersohn
November 1998, Acta pharmaceutica Hungarica,
A Hutchaleelaha, and H H Chow, and M Mayersohn
December 1991, Methods and findings in experimental and clinical pharmacology,
A Hutchaleelaha, and H H Chow, and M Mayersohn
June 1972, Cancer research,
A Hutchaleelaha, and H H Chow, and M Mayersohn
October 2012, Antimicrobial agents and chemotherapy,
A Hutchaleelaha, and H H Chow, and M Mayersohn
July 1990, Cancer research,
A Hutchaleelaha, and H H Chow, and M Mayersohn
January 1996, Toxicology and applied pharmacology,
A Hutchaleelaha, and H H Chow, and M Mayersohn
January 2015, PloS one,
Copied contents to your clipboard!