Metabolic Fate of Clonidine. (IV): Plasma Protein Binding of Clonidine In vitro and In vivo and Transfer to Fetus and Milk in Rats after Subcutaneous Administration of Clonidine.

Abstract

Summary: The plasma protein binding of 14C-clonidine in vitro and in vivo and its transfer into the fetus and milk in rats were investigated.1. The binding ratios of radioactivity in vitro to male rat, dog, monkey and human plasma proteins did not change with drug concentration in any species and no marked species difference was observed, however, in vivo binding to male rat, dog and monkey plasma proteins tended to increase with the elapse of time.2. After subcutaneous administration to pregnant rats at a dose of 1 mg/kg, the radioactivity levels in the fetal kidney and liver were higher than that in the maternal plasma. The radioactivity was rapidly elimi nated from the fetal tissues as that from the maternal plasma. On the whole body autoradiograms, compara ble radioactivity was found in the fetus with the maternal plasma.3. The radioactivity level in the milk reached a maximum at 30 min after subcutaneous administration at a dose of 1 mg/kg, being 5.5 times higher than that in the plasma, but was comparable with that in the plasma after 8 hr and decreased to undetectable level at 72 hr after administration.

A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women

“…d Predicted using physicochemical parameters in Simcyp. Reported B/P ratio in rodents is 1.07 (Yamahata et al, 1996).…”

“…dosing profiles is ;3 l/kg (Frisk-Holmberg et al, 1981). Mean K p values determined in rodents (Conway and Jarrott, 1980;Yamahata et al, 1996) were used, as opposed to predicted K p values, because these values were found to better characterize the biphasic distribution of clonidine in plasma following either i.v. or oral dosing.…”

Metabolic Fate of Clonidine. (V): Metabolism of Clonidine after Subcutaneous Administration of Clonidine to Rats, Dogs and Monkeys and Dermal Application of Clonidine Tape, M-5041T, to Rats.

“…As a part of the investigation on this system, the metabolic fate of clonidine in animals was studied using [imidazolidine-2-14C]clonidine (14C-cloni dine) as a tracer. [1][2][3][4] This paper presents the metabolism of clonidine after subcutaneous administration of 14C clonidine to rats, dogs and a monkey and dermal applica tion of the system containing 14C-clonidine, 14C-M 5041T, to rats. Materials and Methods…”