Pharmcokinetics 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 protector in chemotherapy trials in cancer patients. We studied the pharmacokinetics of NAc-SDKP in six healthy human volunteers and in five patients 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 intra- and interday baseline variations in healthy subjects. The baseline value (range 1.7-3.2 nM) differed between subjects, but was constant over time. The influence of the route of administration was studied in six healthy volunteers with 128 nmol/kg given as a 12-hr intravenous infusion or as a single subcutaneous or intramuscular injection. After cessation of intravenous infusion in healthy volunteers, NAc-SDKP was characterized by a quick elimination phase, with a mean half-life of 4.5 min. The volume distribution was 117 ml/kg and the area under the curve was 117 nM hr. After subcutaneous and intramuscular administrations, peak plasma drug concentrations occurred at 0.26 and 0.28 hr, with Cmax values of 156 and 110 nM, respectively. The bioavailabilities determined after subcutaneous and intramuscular administrations were 100 and 81%, respectively. NAc-SDKP pharmacokinetics was studied in patients after intravenous infusion over 48 hr of a dose of between 51.3 and 513 nmol/kg. Area under the curve values increased proportionately with the dose. Mean clearance was lower in patients than in healthy volunteers: 524 vs. 1120 ml/hr/kg, respectively.
Ezan
E
E
Commissariat à l'Energie Atomique, Service de Pharmacologie et d'Immunologie/DRIPP, Yvette, France.
Carde
P
P
Le Kerneau
J
J
Ardouin
T
T
Thomas
F
F
Isnard
F
F
Deschamps de Paillette
E
E
Grognet
J M
JM
D000328:Adult; D000368:Aged; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*
D009842:Oligopeptides; C058504:goralatide