PHARMACOKINETICS IN HEALTHY-VOLUNTEERS AND PATIENTS OF NAC-SDKP (SERASPENIDE), A NEGATIVE REGULATOR OF HEMATOPOIESIS

NAc-SDKP is a peptide being tested as a bone marrow hematopoiesis prot ector in chemotherapy trials in cancer patients. We studied the pharma cokinetics of NAc-SDKP in six healthy human volunteers and in five pat ients undergoing chemotherapy. Plasma concentrations of NAc-SDKP were monitored using a specific enzyme immunoassay. Because NAc-SDKP is an endogenous compound, a preliminary study was undertaken to determine i ntra- and interday baseline variations in healthy subjects. The baseli ne value (range 1.7-3.2 nM) differed between subjects, but was constan t over time. The influence of the route of administration was studied in six healthy volunteers with 128 nmol/kg given as a 12-hr intravenou s infusion or as a single subcutaneous or intramuscular injection. Aft er cessation of intravenous infusion in healthy volunteers, NAc-SDKP w as characterized by a quick elimination phase, with a mean half-life o f 4.5 min. The volume distribution was 117 ml/kg and the area under th e curve was 117 nM hr. After subcutaneous and intramuscular administra tions, peak plasma drug concentrations occurred at 0.26 and 0.28 hr, w ith C-max values of 156 and 110 nM, respectively. The bioavailabilitie s determined after subcutaneous and intramuscular administrations were 100 and 81%, respectively. NAc-SDKP pharmacokinetics was studied in p atients after intravenous infusion over 48 hr of a dose of between 51. 3 and 513 nmol/kg. Area under the curve values increased proportionate ly with the dose. Mean clearance was lower in patients than in healthy volunteers: 524 vs. 1120 ml/hr/kg, respectively.