Abstract
Gas-uptake pharmacokinetics and metabolism of the chlorofluorocarbon replacement 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) were investigated in rats, mice, and hamsters. Species differences in the rate of uptake of HCFC-124 and urinary excretion of trifluoroacetic acid were observed. In rats and mice, the uptake of HCFC-124 was described by both saturable and first-order components, whereas in the hamster only first-order uptake was observed. The in vivo metabolic rate constants obtained from computer simulation of the gas-uptake data were: for rats-KM = 1.2 mg liter-1 (8.79 mmol liter-1, Vmaxc = 0.35 +/- 0.01 mg kg-1 hr-1 (2.56 +/- 0.01 mmol kg-1 hr-1), and kfc = 1.25 +/- 0.01 hr-1 kg231; for mice-KM = 1.2 mg liter-1 (8.79 mmol liter-1), Vmaxc = 1.78 +/- 0.01 mg kg-1 hr-1 (13.0 +/- 0.007 mmol kg-1 hr-1), and kfc = 4.08 +/- 0.01 hr-1 kg-1; and for hamsters-kfc = 1.47 +/- 0.02 hr-1 kg-1. The production and excretion of trifluoroacetic acid, the major urinary metabolite of HCFC-124, were also simulated in rats and mice, but not in hamsters, by the physiologically based pharmacokinetic model when the in vivo metabolic rate constants obtained in the gas-uptake simulation studies were used. The blood:air partition coefficient of HCFC-124 in the hamster was lower than in the rat or mouse. A low blood:air partition coefficient may limit the pulmonary uptake of volatile chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|