• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.219-226
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• 1990

Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical ($Vasotec^{\circledR}$, 61.38 ng/ml; $Beartec^{\circledR}$, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for $Vasotec^{\circledR}$ and $Beartec^{\circledR}$ tablets are presented in that order; area under the curve=330.63:320.96 $ng{\cdot}hr/ml$; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.271-278
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• 1995

The objective of the present study was to investigate the inhibitory effect of physiologically pulsatile pattern of testosterone(T) on luteinizing hormone(LH) in wethers. To do this, 3 separate experiments were conducted. Infusion rates and patterns needed to produce normal T secretory profiles found in intact rams were established in Experiment 1, the time-course of the suppressive effect of T on circulating LH concentrations was determined in Experiment 2, and the effectiveness of a pulsatile versus a constant pattern of T to suppress LH secretion in wethers was compared in Experiment 3. In Experiment 1, three different doses(25, 50 or $100{\mu}g$) of T were injected intravenously to animals to do pharmacokinetic analysis of T. Elimination rate constant, volume of distribution, and total body clearance of T averaged $0.18min^{-1}$, 0.531/kg BW, and 0.091/min/ kg BW, respectively. In Experiment 2, three different doses(192,384, or $768{\mu}g/kg/24h$) of T were infused at 4h intervals for 3 days into animals to evaluate the time course of the inhibitory effect of T on mean LH concentration. As duration of T infusion increased, mean LH concentrations gradually reduced. Mean LH concentrations were significantly lower at day 2 or day 3 than at day 0. However, mean LH concentrations did not differ between day 0 and day 1 or between day 2 and day 3. In Experiment 3, animals were subjected to two different intravenous infusion regimens for 3 days: constant T($768{\mu}g/kg/24h$) and pulsatile(one pulse every 4h) T($768{\mu}g/kg24h$). Blood samples were collected at 10-min intervals for 4h both prior to infusion and during the last 4h of the infusion. Mean LH was more suppressed(p=0.045) by constant T than by pulsatile T. LH pulse amplitude was not affected by constant T or pulsatile T. LH interpulse interval was increased more(p=0.034) by constant T than pulsatile T.