Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans. 1995

S C Mehta, and D R Lu
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602, USA.

Sodium mercaptoundecahydrododecaborate or BSH is an important compound for boron neutron capture therapy (BNCT). The total clearance and steady state volume of distribution of BSH in humans and in laboratory animals were analyzed as a function of species body weight using the allometric equation for interspecies scaling. Significant linear relationships were obtained between log CLt (Lh-1) and log W (kg) (r = 0.972; p = 0.028) as well as log VSS (L) and log W (kg) (r = 0.999; p = 0.0005). The corresponding allometric equations were CLt = 0.127 W0.68 and VSS = 1.557 W0.87, respectively. BSH clearance in various species was shown to be a constant fraction (0.26) of creatinine clearance, the relationship being independent of body weight. Thus BSH clearance in various species occurred at similar pace when measured by a physiological parameter (creatinine clearance) rather than chronological time. Interspecies scale-up of plasma concentration-time data for the four species using a complex Dedrick plot resulted in similar profiles. Our results indicate that the BSH data obtained in laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters in humans. These parameters can serve as guidelines for better planning of clinical studies.

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
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
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
D001894 Borohydrides A class of inorganic or organic compounds that contain the borohydride (BH4-) anion. Borohydride
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
D013438 Sulfhydryl Compounds Compounds containing the -SH radical. Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D016754 Boron Neutron Capture Therapy A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. Boron-Neutron Capture Therapy,Neutron Capture Therapy, Boron,Therapy, Boron Neutron Capture,Therapy, Boron-Neutron Capture

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