• 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.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.507-515
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• 1996

Background : Potassium channel opener (K-opener) opens ATP-sensitive K'-channel located at cell membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip pre-incubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 kinetics in vivo. Purpose : This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice. Methods : Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use ($5{\times}10^5$ cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or l0uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or $100{\mu}g$ of pinacidil was injected intravenously into ICR mice at 10 min after $5{\mu}Ci$ T1-201 injection, and organ uptake and whole body retention rate were measured at different time points. Results : Co-incubation of pinacidil with T1-201 resulted in a decrease in T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with $100{\mu}g$ of pinacidil than control. Conclusion : These results suggest that treatment with K-opener may affect the interpretation of T1-201 myocardial images, due to decreasing thallium accumulation and enhancing washout from myocardium.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.128-136
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• 2002

Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.