• Journal of fish pathology
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• v.23 no.1
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• pp.57-67
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• 2010

Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of nalidixic acid (NA), piromidic acid (PA) and oxolinic acid (OA) were studied after oral administration to cultured olive flounder, Paralichthys olivaceus. Serum concentrations of these antimicrobials were determined after oral administration of a single dosage of 60 mg/kg body weight (average 700 g). At $23{\pm}1.5^{\circ}C$, the peak serum concentrations of NA, PA and OA, which attained at 10 h, 24 h and 30 h post-dose, were 11.55, 3.79 and $1.12{\mu}g/m\ell$, respectively. At $13{\pm}1.5^{\circ}C$, the peak serum concentrations of NA, PA and OA, which attained at 10 h, 15 h and 30 h post-dose, were 6.36, 1.4 and $1.01{\mu}g/m\ell$, respectively. Better absorption of NA and PA was noted at $23{\pm}1.5^{\circ}C$ compared to $23{\pm}13^{\circ}C$. The elimination of NA from serum of olive flounder was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. However, both absorption and elimination of OA were not affected significantly by temperature. The kinetic profile of absorption, distribution and elimination of these antimicrobials in serum were analyzed by fitting to a one- and two compartment model, with WinNonlin program. In the one compartment model for NA, AUC, Tmax and Cmax at $23{\pm}1.5^{\circ}C$ were $258.26{\mu}g{\cdot}h/m\ell$, 10.67 h and $8.91{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $C_{max}$ at $13{\pm}1.5^{\circ}C$ were $341.45 {\mu}g{\cdot}h/m\ell$, 7.72 h and $6.23{\mu}g/m\ell$, respectively. In the one compartment model for PA, AUC, $T_{max}$ and $C_{max}$ at $23{\pm}1.5^{\circ}C$ were $248.12{\mu}g{\cdot}h/m\ell$, 21.15 h and $3.09{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $C_{max}$ at $13{\pm}1.5^{\circ}C$ were $103.89{\mu}g{\cdot}h/m\ell$, 12.89 h and $1.22{\mu}g/m\ell$, respectively. In the two compartment model for OA, AUC, $T_{max}$ and $C_{max}$ at $23{\pm}1.5^{\circ}C$ were $138.20{\mu}g{\cdot}h/m\ell$, 23.95 h and $1.06{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $T_{max}$ at $13{\pm}1.5^{\circ}C$ were $159.10{\mu}g{\cdot}h/m\ell$, 28.03 h and $1.02{\mu}g/m\ell$, respectively.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.1-7
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• 1987

The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.

• 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.31 no.1
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• pp.19-29
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• 1997

Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential $R_v=k_3/k_4$ using graphic method or $R_A$= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(${\int}^{120min}_0$ BG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(${\int}^{120min}_0$ OCC(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, $R_A$, and $R_v$ which are often assumed that these values reflect the true values of $k_3/k_4$. The rate constants $K_1,\;k_2\;k_3$ and $k_4$ to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing $K_l$ and $k_3$(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, $R_A$, and $R_v$ were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The late constants $K_l,\;k_2\;k_3\;k_4$ at BG and OCC were $1.26{\pm}5.41%,\;0.044{\pm}19.58%,\;0.031{\pm}24.36%,\;0.008{\pm}22.78%$ and $1.36{\pm}4.76%,\;0.170{\pm}6.89%,\;0.007{\pm}23.89%,\;0.007{\pm}45.09%$, respectively. The Sensitivities for ((${\Delta}S/S$)/(${\Delta}k_3/k_3$)) and ((${\Delta}S/S$)/(${\Delta}K_l/K_l$)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0,23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, $R_A$, and $R_v$) with $k_3/k_4$ were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [I-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (3G-OCC)/OCC, $R_A$ or $R_v$ and true $k_3/k_4$, although the slopes between them were not unity. Pharmacokinetic computer simulations may be a very useful technique in studying dopamine transporter systems.