Pharmacokinetics of a hematoregulatory peptide (SK&F 107647) in healthy male volunteers and in patients with colorectal or pancreatic adenocarcinoma not amenable to standard therapy

Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetic hemat oregulatory peptide, in healthy volunteers and in patients with adenocarcin oma. Methods. SK&F 107647 pharmacokinetics were evaluated in 2 dose-escalation s tudies. Volunteers received SK&F 107647 as single 15-minute iv infusion dos es of 1, 10, 100, 500, and 1000 mu g/kg. Cancer patients received 7-hour iv infusions of 0.001, 0.01, 0.1 and 1 mu g/kg once daily for 10 days. Drug c oncentrations were quantified in plasma and urine of healthy volunteers and on days 1 and 10 in plasma of cancer patients receiving the two top dose l evels. Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101 ml/hour /kg; mean volume of distribution at steady-state (V-ss) ranged from 175 to 268 ml/kg. Most of the administered dose was renally excreted as intact pep tide within 24 hours postinfusion. In patients, mean CL was 57.6 ml/hourkg, mean V-ss ranged from 128 to 150 ml/kg and terminal half-life from 2.1 to 3.4 hours. There was little accumulation of drug. In both studies, linear p harmacokinetics was observed. Clearance approached normal glomerular Filtra tion rate (GFR) in volunteers and correlated with creatinine clearance in c ancer patients. Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a small V-ss, an d clearance, primarily renal, approaching normal GFR.