PT  - JOURNAL ARTICLE
AU  - Risa Nasu
AU  - Yoichi Kumagai
AU  - Hirokuni Kogetsu
AU  - Masayuki Tsujimoto
AU  - Hisakazu Ohtani
AU  - Yasufumi Sawada
TI  - PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR PRALMORELIN HYDROCHLORIDE IN RATS
AID  - 10.1124/dmd.104.001040
DP  - 2005 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1488--1494
VI  - 33
IP  - 10
4099  - http://dmd.aspetjournals.org/content/33/10/1488.short
4100  - http://dmd.aspetjournals.org/content/33/10/1488.full
SO  - Drug Metab Dispos2005 Oct 01; 33
AB  - Pralmorelin hydrochloride (pralmorelin), consisting of six amino acid residues, is a growth hormone-releasing peptide. The aim of this study is to analyze the pharmacokinetics of pralmorelin after intravenous bolus administration to rats, and to develop a physiologically based pharmacokinetic (PB-PK) model to describe and predict the concentrations of pralmorelin in blood and tissues. Pralmorelin (3 mg/kg) was administered intravenously to 24 Sprague-Dawley rats. Groups of three rats were sacrificed by decapitation at each designated time point (up to 4 h), and plasma and tissues (brain, lung, heart, liver, kidney, small intestine, muscle, adipose, and skin) were collected. Bile was also pooled until decapitation. The concentration of pralmorelin in samples was determined by liquid chromatography-tandem mass spectrometry. Plasma concentrations of pralmorelin declined rapidly in a biexponential manner. Biliary excretion of pralmorelin was so rapid that 80% of the dose was recovered unchanged in the bile within 1 h after administration. The distribution parameters in each tissue were obtained by using a hybrid model and an integration plot. They revealed that the distribution of pralmorelin into liver was blood flow-limited, and its distribution was permeability-limited in all other tissues. The PB-PK model developed in this study well described the time courses of pralmorelin concentration in the blood and tissues of rats. The American Society for Pharmacology and Experimental Therapeutics