Abstract
Purpose. To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy.
Methods. Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 ng/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human).
Results. In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vdss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a·Wb), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vdss, and T1/2 of SK&F 107647 were 0.63, 0.94, and 0.29, respectively.
Conclusions. Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.
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REFERENCES
J. Mordenti and W. Chappell. The use of interspecies scaling in toxicokinetics. In A. Yacobi, J. Skelly, and V. Batra (eds), Toxicokinetics and New Drug Development, Permagon, New York, 1989, pp. 42–96.
W. R. Chappell and J. Mordenti. Extrapolation of toxicological and pharmacological data from animals to humans. Adv. Drug Res. 20:1–116 (1991).
J. Mordenti, S. A. Chen, J. A. Moore, B. L. Ferraiolo, and J. D. Green. Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm. Res. 8:1351–1359 (1991).
J. Hysing, J. O. Gordeladze G. Christensen, and H. Tolleshaug. Renal uptake and degradation of trapped-label calcitonin. Biochem. Pharmacol. 41:1119–1126 (1991).
T. Maack, C. H. Park, and M. J. F. Gamaro. Renal filtration, transport, and metabolism of proteins. In D. W. Seldin and G. Giesbisch (eds), The kidney, physiology and pathophysiology, 2nd edition, New York, Marcel Dekker, 1992, pp. 3005–3038.
T. Maack, V. Johnson, S. T. Kau, J. Figueiredo, and D. Sigulem. Renal filtration, transport, and metabolism of low-molecular weight proteins. Kidney Int. 16:251–270 (1979).
C. A. Elder, and M. W. Modi. Interspecies scaling of a thienodiazepine platelet-activating factor receptor antagonist. Drug Metabol. Dispos. 23:776–778 (1995).
J. H. Lin. Species similarities and differences in pharmacokinetics. Drug Metabol. Dispos. 23:1008–1021 (1995).
L. M. Pelus, A. G. King, H. E. Broxmeyer, P. L. DeMarsh, S. R. Petteway, and P. Bhatnagar. In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. Exp. Hematol. 22:239–247 (1994).
V. K. Boppana, and C. Miller-Stein. Determination of a novel hematoregulatory peptide in dog plasma by reversed-phase high performance liquid chromatography and an amine-selective ophthaldehyde-thiol post-column reaction with fluorescence detection. J. Chromatogr. 676:161–167 (1994).
D. W. Cockcroft, M. H. Gault. Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41 (1976).
G. D. Allen. MODFIT: A pharmacokinetics computer program. Biopharm. Drug Dispos. 10:477–498 (1990).
B. Davies and T. Morris. Physiological parameters in laboratory animals and humans. Pharm. Res. 10:1093–1095 (1993).
S. Shargel, and A. B. C. Yu. Applied biopharmaceutics and pharmacokinetics. ACC, Norwalk, 1985.
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Brocks, D.R., Freed, M.I., Martin, D.E. et al. Interspecies Pharmacokinetics of a Novel Hematoregulatory Peptide (SK&F 107647) in Rats, Dogs, and Oncologic Patients. Pharm Res 13, 794–797 (1996). https://doi.org/10.1023/A:1016020221300
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DOI: https://doi.org/10.1023/A:1016020221300