• The Korean Journal of Pharmacology
• /
• v.23 no.1
• /
• pp.1-7
• /
• 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
• /
• v.35 no.2
• /
• pp.271-278
• /
• 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.

• Clinical and Experimental Pediatrics
• /
• v.52 no.5
• /
• pp.581-587
• /
• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

• Herbal Formula Science
• /
• v.9 no.1
• /
• pp.231-250
• /
• 2001

In order to determine the effects of annexing bile extracts of bears on the anti-fibrotic effect of Injinhotang. Mix compound of Injinhotang and bile extracts of bears were administered to the carbon tetrachloride ($CCl_4$)-induced cirrhotic rats during 20 days and the changes of serum levels of GOT (glutamic-oxalacetic transaminase), GPT (glutamic pyruvic transaminase), LDH (lactate dehydrogenase), ALP (alanine phosphatase), GGT (gamma glutamyl transpeptidase) and T-BIL (total bilirubin) were monitored with comparison to the results of Injinhotang administered group. The results were summarized as follows. 1. A significant (p<0.01) increase of serum GOT levels were observed in control group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang and Injinhotang with Fel Ursi-administered group. In addition, a significant (p<0.05) increase were also detected In Injinhotang with Fel Ursi-administered group compared to that of Injinhotang-administered group. 2. A significant (p<0.01) increase of serum GPT levels were observed in control group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang and Injinhotang with Fel Ursi-administered group. Although significances were not recorded, increase of serum GPT levels were also detected in Injinhotang with Fel Ursi-administered group compared to that of Injinhotang-administered group. 3. A significant (p<0.01) increase of serum LDH levels were observed in control group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang and Injinhotang with Fel Ursi-administered group. Although significances were not recorded, increase of serum LDH levels were also detected in Injinhotang with Fel Ursi-administered group compared to that of Injinhotang-administered group. 4. A significant (p<0.01 or p<0.05) increase of serum ALP levels were observed in control group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang and Injinhotang with Fel Ursi-administered group. In addition, a significant (p<0.05) increase were also detected in Injinhotang with Fel Ursi-administered group compared to that of Injinhotang-administered group. 5. A significant (p<0.01) increase of serum GGT levels were observed in control and Injinhotang-administered group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang with Fel Ursi-administered group. 6. A significant (p<0.01) increase of serum T-BIL levels were observed in control group compared to those of normal group but these increased levels were dramatically decreased in Injinhotang and Injinhotang with Fel Ursi-administered group. Although significances were not recorded, increase of serum T-BIL levels were also detected in Injinhotang with Fel Ursi-administered group compared to that of Injinhotang-administered group. In conclusion, it is considered that bile extract of bears has some additional effect to the anti-fibrotic effect of Injinhotang but to know the exact mechanism of suitable dose and duration of administration, further studies such as pharmacokinetics and dose-dependent pharmacological studies were needed

• Pediatric Infection and Vaccine
• /
• v.18 no.2
• /
• pp.109-116
• /
• 2011

Purpose : Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model. Methods : Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for ${\beta}$-lactams and macrolide. For the ${\beta}$-lactams, exposure of fT >MIC (time that free drug concentrations remain above the MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model. Results : Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC ${\leq}$1.0 ${\mu}g$/mL and 19 (82.6%) were MIC ${\leq}$2 ${\mu}g$/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC ${\leq}$1.0 ${\mu}g$/mL but PTA decreased to 52% at MIC 2 ${\mu}g$/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 ${\mu}g$/mL. Overall, oral amoxicillin 90 mg/ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion : Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin.

• The Korean Journal of Nuclear Medicine
• /
• v.31 no.1
• /
• pp.19-29
• /
• 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.