caa a22 4500 477127622 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970801xx s 000 0 eng 10.1023/A:1012165731390 doi (NATIONALLICENCE)springer-10.1023/A:1012165731390 Studies on the Mechanism of Absorption of Depot Neuroleptics: Fluphenazine Decanoate in Sesame oil [Elektronische Daten] [Jiang-Ping Luo, John Hubbard, Kamal Midha] Purpose. The purpose of the present study was to investigate the pharmacokinetic characteristics of fluphenazine (FLU) and its decanoate (FLU-D) after intravenous and intramuscular administration to dogs. Methods. A group of four beagle dogs was used in all intravenous and intramuscular experiments, with washout periods of no less than three months between doses. Results. After intravenous FLU-D, the pharmacokinetics of the prodrug (mean ± SD) were as follows: Clearance (CL) 42.9 ± 6.3 L/h; terminal half-life (t1/2) 3.5 ± 0.8 h; volume of distribution (Vd) 216 ± 61 L. The fractional availability of FLU was 1.0 ± 0.2. After intravenous FLU, the volume of distribution of FLU (51 ± 17.8 L) was some 4 fold less than that of the prodrug. Simulations (Stella II) suggested that the rate limiting step was slow formation of FLU from the prodrug in the tissue compartment. After intramuscular FLU-D in sesame oil, the apparent t1/2 of FLU was 9.7 ± 2.0 days whereas after intramuscular FLU base in sesame oil, the apparent t1/2 was only 7.7 ± 3.4 h showing that the absorption of FLU itself from the intramuscular site and proximal lymph nodes is relatively rapid. Conclusions. The rate limiting step after intramuscular FLU-D appeared to be the slow partitioning of the prodrug out of the sesame oil at the injection site and in proximal lymph nodes. Plenum Publishing Corporation, 1997 fluphenazine decanoate nationallicence prodrug nationallicence fluphenazine nationallicence pharmacokinetics nationallicence single dose nationallicence Luo Jiang-Ping College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut Hubbard John College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut Midha Kamal College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1079-1084 0724-8741 14:8<1079 1997 14 11095 https://doi.org/10.1023/A:1012165731390 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012165731390 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Luo Jiang-Ping College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut NATIONALLICENCE 700 1- Hubbard John College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut NATIONALLICENCE 700 1- Midha Kamal College of Pharmacy & Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1079-1084 0724-8741 14:8<1079 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer