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 mg/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 (Vd ss) 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.W(b)), 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, Vd(ss), and T(1/2) 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.
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 mg/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 (Vd ss) 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.W(b)), 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, Vd(ss), and T(1/2) 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.
Authors: P Zia-Amirhosseini; R Z Harris; H C Cowley; J W Valle; D R Citerone; V K Boppana; H Scarffe; P Watson; C B Davis Journal: Pharm Res Date: 2000-04 Impact factor: 4.200