Experimentally, superoxide dismutase (SOD) protects against cytotoxological and histotoxological effects of superoxide anions, which play a fundamental role where inflammatory processes are involved. Currently, only bovine copper containing SOD (Cu-SOD) is available for clinical application in the treatment of patients with various arthritic diseases. The intramuscular route is the principal route to administer usual dosages of bovine Cu-SOD 4 to 32mg, 2 or 3 times weekly. A single dose corresponds to an optimal dose ranging from 30 to 200 micrograms/kg, determined from an established dose-response curve. After intramuscular injection of bovine Cu-SOD 8, 16 and 32mg the peak plasma concentration occurs 4 to 8 hours postdose and is 0.05, 0.16 and 0.39 mg/L, respectively. Clinically this metallo-protein is particularly effective for the treatment of inflammation and toxicity resulting from ionising irradiations, ischaemia and tumours. The major advantages of liposomally encapsulated bovine Cu-SOD are its improved pharmacokinetic characteristics, leading to a longer plasma half-life and a slower release of free bovine Cu-SOD. In humans, bovine Cu-SOD (free or liposomal), although a foreign protein, is well tolerated and produces no acute or delayed toxic effects.
The purpose of the present study was to investigate whether the time of day (24 h) at which carbamazepine is administered influences its pharmacokinetics in the rat. The pharmacokinetics of a single, 100 mg . kg-1 bodyweight per os, dose of carbamazepine were studied at four different fixed time points of a 24-hour period (i.e. 10.00, 16.00, 22.00 or 04.00 h) in Wistar AF-SPF adult male rats maintained under controlled environmental conditions (LD: 18.00 - 06.00h) during October 1978. The total plasma levels and the unbound fraction were measured according to an immunoenzymatic method (EMIT). The effects of fasting were also investigated. The data shows circadian variations of pharmacokinetic parameters: the maximum peak concentration and the maximum time to reach this peak was observed when the drug was given respectively at 16.00h and at 10.00h. The elimination half-life varied from 15.15 hours at 16.00h to 10.48 hours at 22.00h. The observed variations may be related to: daily fluctuations of absorption or binding of the drug; diurnal variations of the hepatic drug metabolizing enzymes responsible for the inactivation; and/or diurnal variations in excretion rate of the drug.
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