INTERSPECIES PHARMACOKINETICS OF A NOVEL HEMATOREGULATORY PEPTIDE (SK-AND-F-107647) IN RATS, DOGS, AND ONCOLOGIC PATIENTS

Purpose. To study the pharmacokinetics of SK&F 107647, a novel hemator egulatory agent, in rats, dogs, and patients with non-lymphoid solid t umor malignancy.Methods. Sprague Dawley rats and beagle dogs (n = 6 ea ch; 3 M, 3 Fl were given 25 mg/kg of SK&F 107467 as an iv bolus inject ion, and patients (n = 6; 4 M, 2 Fl 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 th e volume of distribution (Vd(ss)) was reflective of distribution to ex tracellular body water. The plasma CL in humans was near that of avera ge glomerular filtration rate. Using allometric equations for interspe cies scaling (Y = a . W-b), body-weight normalized human pharmacokinet ic data were reasonably predicted using either the body weight normali zed rat or the dog data. The allometric exponents (b) for CL, Vd(ss), and T-1/2 Of SK&F 107647 were 0.63, 0.94, and 0.29, respectively. Conc lusions. Use of a limited pool of available animal data allowed for re asonable predictions of human pharmacokinetics of SK&F 107647.