Scaling Basic Toxicokinetic Parameters from Rat to Man

Overview

Journal Environ Health Perspect

Date 1996 Apr 1

PMID 8732950

Citations 20

Authors

K Bachmann

D Pardoe

D White

Affiliations

Soon will be listed here.

Abstract

Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinical trials of investigational new drugs. Current strategies for scaling either doses of xenobiotics or the dispositional parameters of xenobiotics from animals to man rely on models that take account principally of species differences in weight or body surface area. Interspecies scaling of dispositional parameters such as clearance or volume of distribution commonly involves the comparison of estimates of these parameters for a given xenobiotic among numerous species on the basis of weight with the resultant mathematical relationship used to predict the values of those parameters for that xenobiotic in a species weighing, on average, about 70 kg (i.e., a man). Our approach has been to ascertain whether a useful mathematical model could be developed for predicting the dispositional parameters of a xenobiotic, its half-life and volume of distribution, in humans based exclusively on estimates of those parameters in rats. Based on a data set of about 100 different xenobiotics, we found that values for half-life and volume of distribution of a xenobiotic in humans can be predicted from the estimates of those parameters in rats.

Citing Articles

Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study.

Beraldi-Magalhaes F, Parker S, Sanches C, Garcia L, Souza Carvalho B, Fachi M Antibiotics (Basel). 2021; 10(12).

PMID: 34943771 PMC: 8698281. DOI: 10.3390/antibiotics10121559.

Animal to human translation: a systematic scoping review of reported concordance rates.

Leenaars C, Kouwenaar C, Stafleu F, Bleich A, Ritskes-Hoitinga M, De Vries R J Transl Med. 2019; 17(1):223.

PMID: 31307492 PMC: 6631915. DOI: 10.1186/s12967-019-1976-2.

Low-Dose Curcumin Nanoparticles Normalise Blood Pressure in Male Wistar Rats with Diet-Induced Metabolic Syndrome.

du Preez R, Pahl J, Arora M, Kumar M, Brown L, Panchal S Nutrients. 2019; 11(7).

PMID: 31288419 PMC: 6682951. DOI: 10.3390/nu11071542.

A microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles.

Li L, Gokduman K, Gokaltun A, Yarmush M, Usta O Nanomedicine (Lond). 2019; 14(16):2209-2226.

PMID: 31179822 PMC: 7006797. DOI: 10.2217/nnm-2019-0086.

Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling.

Choi G, Lee Y, Cho H Pharmaceutics. 2019; 11(4).

PMID: 30959827 PMC: 6523982. DOI: 10.3390/pharmaceutics11040168.

References

Fujioka Y, Mizuno N, Morita E, Motozono H, Takahashi K, Yamanaka Y . Effect of age on the gastrointestinal absorption of acyclovir in rats. J Pharm Pharmacol. 1991; 43(7):465-9. DOI: 10.1111/j.2042-7158.1991.tb03515.x. View

Aarons L, Mandema J, Danhof M . A population analysis of the pharmacokinetics and pharmacodynamics of midazolam in the rat. J Pharmacokinet Biopharm. 1991; 19(5):485-96. DOI: 10.1007/BF01062959. View

Dickinson R, Baker P, Franklin M, Hooper W . Facile hydrolysis of mebeverine in vitro and in vivo: negligible circulating concentrations of the drug after oral administration. J Pharm Sci. 1991; 80(10):952-7. DOI: 10.1002/jps.2600801010. View

Kean W, Antal E, Grace E, Cauvier H, Rischke J, BUCHANAN W . The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis. J Clin Pharmacol. 1992; 32(1):41-8. DOI: 10.1002/j.1552-4604.1992.tb03786.x. View

Adusumalli V, Yang J, Wong K, KUCHARCZYK N, Sofia R . Felbamate pharmacokinetics in the rat, rabbit, and dog. Drug Metab Dispos. 1991; 19(6):1116-25. View

Shobha J, Raghuram T, Kumar A, Krishnaswamy K . Antipyrine kinetics in undernourished diabetics. Eur J Clin Pharmacol. 1991; 41(4):359-61. DOI: 10.1007/BF00314968. View

Bhargava H, Villar V . Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. J Pharmacol Exp Ther. 1992; 261(1):290-6. View

Mandema J, Tukker E, De Boer A, Danhof M . Modeling of the effect site equilibration kinetics and pharmacodynamics of racemic baclofen and its enantiomers using quantitative EEG effect measures. J Pharmacol Exp Ther. 1992; 261(1):88-95. View

Puigdemont A, Guitart R, De Mora F, Arboix M . Prediction of the disposition of propafenone in humans and dogs from pharmacokinetic parameters in other animal species. J Pharm Sci. 1991; 80(12):1106-9. DOI: 10.1002/jps.2600801203. View

10.

Isert D, Klesel N, Limbert M, Markus A, Seibert G, Schrinner E . Pharmacokinetics of cefpirome administered intravenously or intramuscularly to rats and dogs. J Antimicrob Chemother. 1992; 29 Suppl A:31-7. DOI: 10.1093/jac/29.suppl_a.31. View

11.

Kinoshita H, Ohishi N, Kato M, Tokura S, Okazaki A . Pharmacokinetics and distribution of recombinant erythropoietin in rats. Arzneimittelforschung. 1992; 42(2):174-8. View

12.

Chien D, Sandri R . Systemic pharmacokinetics of acitretin, etretinate, isotretinoin, and acetylenic retinoids in guinea pigs and obese rats. Drug Metab Dispos. 1992; 20(2):211-7. View

13.

Miyake K, Fukuchi H, Kitaura T, Kimura M, Kimura Y . Pharmacokinetic analysis of amitriptyline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of amitriptyline. J Pharmacobiodyn. 1992; 15(4):157-66. DOI: 10.1248/bpb1978.15.157. View

14.

Andersen M, Krishnan K, Conolly R, MCCLELLAN R . Biologically based modeling in toxicology research. Arch Toxicol Suppl. 1992; 15:217-27. DOI: 10.1007/978-3-642-77260-3_29. View

15.

Hori R, He Y, Shima T, Inui K, Aoki S, Okumura K . Total body and hepatic clearance in rats of recombinant tissue-type plasminogen activator expressed in mouse C127 and Chinese hamster ovary cells. Drug Metab Dispos. 1992; 20(4):541-6. View

16.

Tsunekawa Y, Hasegawa T, Nadai M, Takagi K, Nabeshima T . Interspecies differences and scaling for the pharmacokinetics of xanthine derivatives. J Pharm Pharmacol. 1992; 44(7):594-9. DOI: 10.1111/j.2042-7158.1992.tb05471.x. View

17.

Kurihara A, Naganuma H, Hisaoka M, Tokiwa H, Kawahara Y . Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data. Antimicrob Agents Chemother. 1992; 36(9):1810-6. PMC: 192191. DOI: 10.1128/AAC.36.9.1810. View

18.

Sabater J, Domenech J, Obach R . Pharmacokinetic study of tolmetin in the rat. Arzneimittelforschung. 1992; 42(7):950-3. View

19.

Nakashima E, Matsushita R, Takeda M, Nakanishi T, ICHIMURA F . Comparative pharmacokinetics of cefoperazone and cephradine in untreated streptozotocin diabetic rats. Drug Metab Dispos. 1992; 20(5):730-5. View

20.

Bachmann K, Chu C, Greear V . In vivo evidence that ethosuximide is a substrate for cytochrome P450IIIA. Pharmacology. 1992; 45(3):121-8. DOI: 10.1159/000138990. View