Pharmacokinetics and pharmacodynamics of methylphenidate enantiomers in rats

We investigated the relationships between methylphenidate (MPD) enantiomers and endogenous dopamine (DA) levels in striatal extracellular fluid, and that between DA level and locomotor activity, after intravenous administration of racemic MPD (2,5 or 10 mg/kg dose) or the individual enantiomers (2.5 mg/kg dose) to rats. MPD and DA levels in the extracellular fluid were measured by in vivo brain microdialysis. The maximum levels of MPD enantiomers in the striatal extracellular fluid were obtained within 15 min after administration. On the other hand, the mean maximum DA levels after administration of 2–10 mg/kg dose of racemic MPD were obtained within 10 min with values in the range of 3.0- to 8.6- fold higher than the basal DA level. The maximum DA level (4.2-fold of the basal level) after administration of (+)-MPD was greater than that (2.2-fold) of the same dose of (−)-MPD. A clockwise hysteresis was observed between MPD concentration and DA level in the extracellular fluid after MPD administration. Locomotor activity after administration of (+)-MPD was also greater than (−)-MPD. From these results, it was shown that the locomotor activity induced by MPD may be related to the increase of DA level in the extracellular fluid, and the degree of increase of the DA level by (+)-MPD was greater than that of the (−)-isomer.     

Pharmacokinetics of methylphenidate in hyperkinetic children.

1 Pharmacokinetic study has been carried out following oral administration of 10-20 mg of methylphenidate hydrochloride to four behaviorally disorders children. 2 It is indicated that the drug is metabolized to ritalinic acid with an apparent plasma half life of 2.5 h. 3 The variability in magnitude of plasma concentration seems to be due not to its metabolism to ritalinic acid but due to the variability in the apparent volume of distribution. 4 The brief half life of methylphenidate which parallels the short duration of action of methylphenidate in behaviorally disordered children may be explained in part by its low protein binding which results in high percentage of free drug being made available for metabolism to pharmacologically inactive metabolites.     

盐酸哌甲酯缓释微丸胶囊剂家兔体内药动学及生物等效性研究

目的:考察自制盐酸哌甲酯缓释微丸胶囊剂在家兔体内的药动学过程,并对其相对生物利用度进行初步研究.方法:采用两周期交叉设计,8只家兔单剂量口服18 mg自制盐酸哌甲酯缓释微丸胶囊剂和市售盐酸哌甲酯控释片为参比制剂,分别于服药前、服药后0.5、1、2、3、4、6、8、10、12、24和32 h采血,以HPLC-二级质谱联用法(LC/MS/MS)测定盐酸哌甲酯不同时间点的血浆浓度,并进行统计学处理.结果:LC/MS/MS法测定盐酸哌甲酯血药浓度最低检测限可达到0.06 ng/ml.两种制剂在家兔体内的药-时曲线均呈双峰,其中自制盐酸哌甲酯缓释微丸胶囊剂tmax1＝(1.02±0.04) h,tmax2＝(5.98±0.03) h,cmax1＝(0.82±0.22) ng/ml,cmax2＝(1.54±0.33) ng/ml;参比制剂tmax1＝(0.50±0.02) h,tmax2＝(3.96±0.03) h,cmax1＝(0.45±0.12) ng/ml,cmax2＝(1.25±0.29) ng/ml.与参比制剂相比,自制盐酸哌甲酯缓释微丸胶囊剂两峰的达峰时间更晚,峰浓度更大,两制剂间有显著性差异(P<0.05).结论:自制盐酸哌甲酯缓释微丸胶囊剂生物利用度优于参比制剂.     

Pharmacokinetics of methylphenidate after oral administration of two modified-release formulations in healthy adults

OBJECTIVE: To compare the rate and extent of absorption of DL-threo-methylphenidate (MPH) from two modified-release MPH formulations at their respective recommended starting doses in healthy adult volunteers. DESIGN: Open-label, randomised, crossover, bioavailability study. PARTICIPANTS: Twenty healthy adult male and female volunteers. METHODS: Subjects received single doses of two modified-release formulations of MPH, a 20mg capsule (Ritalin) LA) and an 18 mg tablet (Concerta). A total of 19 plasma samples was collected over 24 hours, and MPH plasma concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS). These values were used to calculate standard noncompartmental pharmacokinetic parameters describing the rate (peak concentration and time to peak concentration) and extent (area under the concentration-time curve, AUC) of absorption of the two formulations. The relative bioavailability of the two drugs was assessed using a 90% confidence interval, based on the lower and upper endpoints of the confidence interval for the ratios of the geometric means (log transformed) being within the 0.80-1.25 equivalence criterion. RESULTS: Nineteen subjects, ten male and nine female, aged 21-34 years completed both treatment phases of the study. The Ritalin LA formulation displayed a distinctly biphasic pharmacokinetic profile, with mean initial peak plasma concentration of 7 microg/L at an average of 2.1 hours after administration and a second peak of 9.3 microg/L occurring at 5.6 hours. In contrast, the profile of the Concerta formulation rapidly reached an initial plateau concentration of 3.4 microg/L at 3.3 hours after administration and a second mean plateau concentration of 5.9 microg/L approximately 6 hours after administration. Substantially more MPH was absorbed from Ritalin LA than from Concert over the first 4 hours; the respective AUC(4) values were 18.5 and 9.3 microg x h/L (p < 0.001). The overall extent of absorption of MPH was similar between the two formulations. Oral clearance was identical between the two dosage forms. CONCLUSIONS: The Ritalin LA formulation exhibited more rapid initial absorption and reached significantly higher peak plasma concentrations compared with the Concerta formulation, although the oral bioavailability of MPH was similar between the two formulations. The Ritalin LA capsule demonstrated a distinctly bimodal plasma concentration-time profile. MPH plasma concentrations resulting from Concerta reached a peak at 6 hours. These results indicate that the recommended starting dose of the Ritalin LA 20 mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18 mg starting dose of the Concerta formulation.     

依立托仑的药动学特点和临床应用展望

依立托仑是脂多糖(LPS)的毒性中心脂质A的结构模型,内毒素的拮抗药。其作用具有剂量依赖性,能不同程度阻断LPS诱导的活化反应,抑制细胞因子的产生,有效地改善内毒素引起的临床症状和体征,抑制体外循环心脏手术后的炎症反应,且动物实验和人体试验均没有LPS激动效应,这种制剂有可能用于治疗由LPS引起的各种疾病。本文综述了依立托仑的药动学特征和在心血管手术方面的应用前景。     

头孢妥仑匹酯的药动学和临床评价

头孢妥仑匹酯片是我国上世纪90年代批准的一类新药,具有强大的抗革兰阳性（GP）和革兰阴性（GN）菌活性,现已被划归为第4代口服头孢菌素.本文主要概述头孢妥仑匹酯的药动学和临床评价.     

右旋兰索拉唑双相控释制剂的药动学研究及其临床疗效

右旋兰索拉唑是兰索拉唑的右旋对映体,其有更好的药动学性质,如平均滞留时间更长、消除速率远小于消旋体.右旋兰索拉唑双相控释制剂有其独特的双相控释模式,能较好解决在一个给药周期内有效控制胃酸的问题.本文拟在国外研究的基础上,综述右旋兰索拉唑双相控释制剂药动学研究和临床疗效.     

Pharmacokinetics and clinical evaluation of ceftriaxone in neonates

A parenteral cephem antibiotic ceftriaxone (CTRX) was studied for its pharmacokinetic features and clinical efficacy and safety in various infections in neonates including premature infants at 11 institutions associated with Japan Perinatal Infection Research Group. The following results obtained are summarized as follows. 1. Following single intravenous bolus injections with 10 and 20 mg/kg of CTRX, serum levels of the drug at 30 minutes post-dose 36-42 micrograms/ml and 46-76 micrograms/ml, respectively, and those at 12 hours post-dose were 10-14 micrograms/ml and 13-21 micrograms/ml, respectively, in a total of 105 neonates. Serum levels detected were on very gentle descending curves. 2. Half-lives (T 1/2) of the drug in serum were significantly prolonged in 0-3 day age groups of both mature and premature infants: it was especially long in premature infants with age of 0-3 days; i.e., 17.1 hours. There was no difference in T 1/2 between the 4-7 day and 8-28 day age groups. 3. Urinary excretion rates were 20-30% in the first 6 hours post-dose and 30-40% in 12 hours post-dose, in 80 neonates examined. 4. Clinical efficacy: Clinical efficacies were evaluated in 112 of 168 enrolled excluding infants with 90 days of age or older, who were treated for prophylaxis and unevaluable cases. The safety was evaluated in 161 of the 168. (1) Demographic background of the 112 cases: The 112 cases were composed of 89 neonates with ages of 28 days or younger, 21 premature infants, 57 males and 55 females. The drug was given to 102 of the cases by intravenous bolus injection, with 81 cases administered twice a day and 97 cases receiving 10-50 mg/kg a day. (2) Efficacy rate in the 112 cases: In 60 cases for whom causative pathogens were identified the efficacy rate was 90.0% in total (excellent: 31/60; good: 23/60); efficacy rates of 87.5% were obtained in 8 cases with purulent meningitis and 90.9% in 11 with septicemia. In 52 with causative pathogen not identified, the efficacy rate was 96.2% in total (excellent: 21/52; good: 29/52). (3) Adverse reaction: Adverse reactions were noted in 14 of the 161 cases where the safety was evaluated (8.7%). These reactions included diarrhea in 11, vomiting in 2 and exanthema in 1. Abnormalities in laboratory test values were observed in 25 of the 152 cases (16.4%). They included eosinophilia in 14, elevated GOT in 4 and thrombocytosis in 3 etc.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and clinical effects of cefixime in pediatrics

Pharmacokinetics and clinical effects of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows. CFIX (5% granules) was given to each of 5 children twice in a single dose of 1.5 or 3.0 mg/kg in a cross-over trial. The mean peak serum concentration of CFIX was 0.64 micrograms/ml at 4 hours after given the dose of 1.5 mg/kg and 1.15 micrograms/ml at 4 hours after the dose of 3.0 mg/kg. The mean half-life and the mean AUC values were 2.72 hours and 4.10 micrograms X hr/ml, respectively after the dose of 1.5 mg/kg, and 2.77 hours and 8.26 micrograms X hr/ml after the dose of 3.0 mg/kg. The urinary recovery was investigated in 5 children after the dose of CFIX of 1.5 mg/kg and in 4 children after the dose of 3.0 mg/kg. The mean peak urinary concentrations of CFIX and the mean 12-hour urinary recovery rates were 10.6-67.9 micrograms/ml at 2-10 hours and 15.7% after the dose of 1.5 mg/kg, and were and were 6.16-230 micrograms/ml at 2-8 hours and 18.9% after the dose of 3.0 mg/kg, respectively. CFIX was given to 6 children twice in a single dose of 50 mg either in the form of 5% granules or in capsules in a cross-over trial. The mean peak serum concentrations, half-life and AUC values were 1.26 micrograms/ml at 4 hours, 3.09 hours and 9.63 micrograms X hr/ml, respectively after the dose of 50 mg CFIX in 5% granules, and were 1.16 micrograms/ml at 4 hours, 2.87 hours, and 7.82 micrograms X hr/ml, respectively after the dose of 50 mg in capsules. The urinary recovery was investigated in 5 children. The mean peak urinary concentrations and the mean 12-hour urinary recovery rates were 19.1-114 micrograms/ml at 4-10 hours and 15.7%, respectively after the dose of 50 mg in 5% granules, and were 8.16-89.0 micrograms/ml at 4-10 hours and 11.3%, respectively after the dose of 50 mg in capsules. Clinical efficacy of CFIX was investigated in a total of 26 children including 2 with tonsillitis, 2 with acute bronchitis, 2 with scarlet fever and 20 with urinary tract infection. Each of children were given orally a dose of 2.6 mg/kg CFIX 2-3 times a day for 11 days in average.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetics and pharmacodynamics in clinical use of scopolamine

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine] competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity, primarily for its effect on the eye, gastrointestinal tract, heart, and salivary and bronchial secretion glands, and in special circumstances for a CNS action. Therefore, scopolamine is most suitable for premedication before anesthesia and for antiemetic effects. This alkaloid is the most effective single agent to prevent motion sickness. Scopolamine was the first drug to be made commercially available in a transdermal therapeutic system (TTS-patch) delivering alkaloid. Recently, pharmacokinetic data on scopolamine in different biozlogic matrices were obtained most efficiently using liquid chromatographic-tandem mass spectrometric (LC-MS/MS) or gas chromatography online coupled to mass spectrometry. Pharmacokinetic parameters are dependent on the dosage form (oral dose, tablets; parenteral application; IV infusion; SC and IM injection). Scopolamine has a limited bioavailability if orally administered. The maximum drug concentration occurs approximately 0.5 hours after oral administration. Because only 2.6% of nonmetabolized L-(-)-scopolamine is excreted in urine, a first-pass metabolism is suggested to occur after oral administration of scopolamine. Because of its short half-life in plasma and dose-dependent adverse effects (in particular hallucinations and the less serious reactions, eg, vertigo, dry mouth, drowsiness), the clinical use of scopolamine administered orally or parenterally is limited. To minimize the relatively high incidence of side effects, the transdermal dosage form has been developed. The commercially available TTS-patch contains a 1.5-mg drug reservoir and a priming dose (140 microg) to reach the steady-state concentration of scopolamine quickly. The patch releases 0.5 mg alkaloid over a period of 3 days (releasing rate 5 microg/h). Following the transdermal application of scopolamine, the plasma concentrations of the drug indicate major interindividual variations. Peak plasma concentrations (Cmax) of approximately 100 pg/mL (range 11-240 pg/mL) of the alkaloid are reached after about 8 hours and achieve steady state. During a period of 72 hours the plaster releases scopolamine, so constantly high plasma levels (concentration range 56-245 pg/mL) are obtained, followed by a plateau of urinary scopolamine excretion. Although scopolamine has been used in clinical practice for many years, data concerning its metabolism and the renal excretion in man are limited. After incubation with beta-glucuronidase and sulfatase, the recovery of scopolamine in human urine increased from 3% to approximately 30% of the drug dose (intravenously administered). According to these results from enzymatic hydrolysis of scopolamine metabolites, the glucuronide conjugation of scopolamine could be the relevant pathway in healthy volunteers. However, scopolamine metabolism in man has not been verified stringently. An elucidation of the chemical structures of the metabolites extracted from human urine is still lacking. Scopolamine has been shown to undergo an oxidative demethylation during incubation with CYP3A (cytochrome P-450 subfamily). To inhibit the CYP3A located in the intestinal mucosa, components of grapefruit juice are very suitable. When scopolamine was administered together with 150 mL grapefruit juice, the alkaloid concentrations continued to increase, resulting in an evident prolongation of tmax (59.5 +/- 25.0 minutes; P < 0.001). The AUC0-24h values of scopolamine were higher during the grapefruit juice period. They reached approximately 142% of the values associated with the control group (P < 0.005). Consequently, the related absolute bioavailabilities (range 6% to 37%) were significantly higher than the corresponding values of the drug orally administered together with water (range 3% to 27%). The effect of the alkaloid on quantitative electroencephalogram (qEEG) and cognitive performance correlated with pharmacokinetics was shown in studies with healthy volunteers. From pharmacokinetic-pharmacodynamic modeling techniques, a direct correlation between serum concentrations of scopolamine and changes in total power in alpha-frequency band (EEG) in healthy volunteers was provided.The alkaloid readily crosses the placenta. Therefore, scopolamine should be administered to pregnant women only under observation. The drug is compatible with nursing and is considered to be nonteratogenic.In conclusion, scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting associated with motion sickness. Pharmacokinetics and pharmacodynamics of scopolamine depend on the dosage form. Effects on different cognitive functions have been extensively documented.     

Pharmacokinetics and clinical safety of aztreonam in neonates

Clinical pharmacology and safety of aztreonam (AZT) in the neonatal period were investigated. The results obtained are summarized as follows. 1. Serum concentrations of AZT at 30 minutes after administration of 10 mg/kg were 22.1-32.2 micrograms/ml and those of 20 mg/kg 22.5-75.9 micrograms/ml. 2. Serum half-lives of AZT were 3.5-6.6 hours in 0-3 day-old neonates, and 2.0-4.0 hours in neonates 4 day-old or older. 3. A dose response was evident between the 10 mg/kg administration group and the 20 mg/kg group. 4. Urinary recovery rates of AZT in the first 6 hours after administration ranged between 17.8 and 69.9%. 5. No clinical side effects were observed in the administration of AZT alone (6 cases), or in combination with ampicillin (9 cases). Thrombocytosis was observed in 1 case as an abnormal laboratory finding, but it returned to normal within 1 week after the completion of AZT administration. 6. AZT had a potent antimicrobial activity against Gram-negative aerobes and hardly induced beta-lactamase. Furthermore, side effects were not observed in this study. Therefore, AZT is considered to be useful for the treatment of urinary tract infections and other serious infections caused by Gram-negative pathogens even in the neonatal period.     

Pharmacokinetics and clinical evaluation of aztreonam in pediatrics

Pharmacokinetics, in vitro, and in vivo effect of aztreonam (SQ 26,776, AZT), a newly synthesized monobactam antibiotic, were investigated in pediatric patients. The pharmacokinetics were studied in 12 children without renal or hepatic impairment, each of whom received single 10, 20 and 40 mg/kg intravenous doses of drug. Serial samples of serum and urine were assayed for AZT. Serum pharmacokinetics of AZT were described by an open, linear, two-compartment kinetic model. After intravenous administration, AZT was eliminated primarily by urinary excretion of unchanged drug (60.4%). The average biological half-lives of AZT in serum were 1.33 (10 mg/kg, n = 1), 1.69 +/- 0.40 (20 mg/kg, n = 8), and 1.51 +/- 0.61 (40 mg/kg, n = 3) hours. The antibacterial activity of AZT against E. coli and P. aeruginosa was equal or slightly stronger than that of CPZ, LMOX, and CTX. It had no antimicrobial activity against Gram-positive cocci. In vivo effect of AZT was evaluated in 13 children with various infections. The result was excellent in 7 cases, good in 1 case, fair in 3 cases and poor in 1 case, with effective ratio of 66.7%. Exanthema or elevation of GOT and GPT were noticed in 3 patients.     

Pharmacokinetics and clinical evaluation of cefpirome in children

Pharmacokinetics and clinical effects of cefpirome (CPR, HR 810) in children were studied. When 20 mg/kg and 40 mg/kg doses of CPR were administered to 4 children through 30 minutes' drip infusion, half-lives were 1.23 +/- 0.23 (mean +/- S.D.) hours and 1.37 +/- 0.35 (mean +/- S.D.) hours, respectively for the 2 dose levels, and recovery rates in urine in the first 6 hours after administration were 74.8% and 56.1%, respectively. CPR was administered to 15 cases (3 tonsillitis, 3 bronchitis, 5 bronchopneumonia, 1 acute cystitis, 1 coxoiliatitis, 1 otitis media, 1 otitis externa). The efficacy rate was 86.7%. Seven strains of bacteria were isolated and identified 4 Haemophilus influenzae, 3 Staphylococcus aureus, 1 Pseudomonas sp. from these cases. These bacteria in children were followed after administration of CPR. Six strains were eradicated and one was reduced in number. No adverse effects of CPR were observed except in 2 cases, one of which showed transient eosinophilia and the other showed a transient increase of transaminase. These results suggest that CPR may be an effective and safe drug to use on children clinically.     

Photophobia and methylphenidate

It is a report of the case of a 7-year-old boy with attention-deficit hyperactive disorder (ADHD), who developed bilateral photophobia when taking methylphenidate (MPH). MPH was stopped and reintroduced many times, and on all of the trials, photophobia reappeared immediately. Photophobia might be an adverse effect of MPH that bothers ADHD children. With the consideration that MPH increases cortical excitability, it is possible that MPH increases sensitivity to some stimulus such as light, and these sensitivities make these children more irritable and sad.     

Pharmacokinetics and clinical studies on cefsulodin in neonates

Pharmacokinetics and clinical studies on cefsulodin (CFS) were conducted in neonates. 1. MIC's of CFS, sulbenicillin and gentamicin (GM) were determined using 7 strains of Pseudomonas aeruginosa clinically isolated from neonates and maintained as stock cultures. CFS was found to be nearly as active as GM. 2. When CFS 20 mg/kg was administered to a 12-day-old neonate by intravenous bolus injection, serum concentrations were 8.7 micrograms/ml before administration and 51.7 micrograms/ml at 30 minutes, 44.4 micrograms/ml at 1 hour, 38.6 micrograms/ml at 2 hours and 11.1 micrograms/ml at 6 hours after administration. The half-life was 2.5 hours. 3. CFS was administered alone or combination with other drugs to 3 neonates. The drug was clinically effective in 2 cases and slightly effective in another. Bacteriologically, one case was rated as decreased, another as replaced, and the remaining one as unchanged. 4. Neither side effects nor abnormal laboratory values attributable to CFS were found.     

Pharmacokinetics and clinical studies on aztreonam in neonates

Pharmacokinetic and clinical studies on aztreonam (AZT) were performed in neonates. Serum concentrations and urinary excretion of AZT were determined in 12 neonates with ages between 0 and 7 days (birth weights were between 1,260 and 3,500 g) upon intravenous injection or 1 hour drip intravenous infusion of AZT at 20 mg/kg. Serum concentrations of AZT at 1 hour after i.v. administration were 54.0 +/- 12.5 micrograms/ml, and half-lives were 6.01 +/- 0.70 hours. Serum concentrations of AZT reached their peaks at the end of drip infusion with levels of 42.1 +/- 17.6 micrograms/ml in the d.i.v. group and half-lives were 6.40 +/- 1.88 hours. Urinary recovery rates in the first 12 hours after administration were 28.5 +/- 6.4% for the i.v. group and 32.3 +/- 13.9% for the d.i.v. group. AZT was administered to 12 neonatal patients (2 cases of sepsis, 2 cases of suspected sepsis, 3 cases of pneumonia, 2 cases of urinary tract infection and 3 cases for prophylaxis), and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. Clinical efficacies in 9 cases except 3 cases with prophylactic use were excellent in 1 case, good in 5 cases, fair in 1 case, poor in 1 case and unknown in 1 case, thus the efficacy rate was 75%. Bacteriological effects in 3 strains with Gram-negative bacilli were eradicated in 2 strains and unchanged in 1 strain, hence the bacteriological eradication rate was 66.7%. Increased GOT and GPT were observed in 1 cases as abnormal laboratory test results, but the abnormality was not serious.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and clinical evaluation of ceftriaxone in pediatric surgery

Pharmacokinetics and clinical studies on ceftriaxone (CTRX) in pediatric surgery were performed and the results obtained are summarized below. 1. In neonates, serum and urinary levels of CTRX were measured in 4 patients following injection (CTRX 20 mg/kg, intravenous bolus injection). Highest levels in serum were observed at 15 or 30 minutes, 59.4-212.5 micrograms/ml. Serum levels of CTRX then decreased very slowly, and serum half-lives (T 1/2) were 7.9-27.1 hours. Urinary recovery rates were 17.0-54.7% in 12 hours. 2. Bile levels of CTRX were also measured in 8 patients with congenital biliary atresia and a patient with congenital biliary dilatation (CBD). Highest levels of CTRX in bile, 10.2 and 13.2 micrograms/ml, were noted in 2 hours following injection to 2 patients. But in other patients, CTRX was undetectable in bile. Recovery rate in bile in 12 hours in a CBD patient was 0.19%. 3. The CTRX was administered to 7 patients (a case of infected lung cyst, 2 cases of peritonitis and 4 cases as prophylaxis to postoperative infection). Clinical results were good in all cases. No clinical and laboratory adverse reaction due to the administration of CTRX was observed. It is concluded that CTRX is a safe and effective antibiotic in pediatric surgery. However, care has to be practiced in determining dosage and interval of CTRX administration because of its pharmacokinetical characteristics.     

Pharmacokinetics and clinical effects of aspoxicillin in pediatric patients

Since the efficacy and the safety of aspoxicillin (ASPC, TA-058) have been established on adult patients and the need of ASPC use on pediatric patients was anticipated, we performed a 16 center study on the clinical utility of ASPC in pediatric patients. 1. Pharmacokinetics ASPC was intravenously administered to 45 patients at a dose of 10, 20 or 40 mg/kg by one shot. Serum concentrations of ASPC were dependent of dose levels, and maximum levels of 58.4-230.8 micrograms/ml and half-lives (beta) of 1.08-1.16 hours were observed. Urinary recovery rates were 62.7-67.2% in 6 hours. Results obtained upon drip infusions (0.5-1 hour) were similar to one shot injections. 2. Clinical results (1) Clinical effectiveness Of 318 evaluable patients including 175 boys and 143 girls, 18.2% were nurslings and 61% were young children under 4 years of age. One hundred eighty six patients from whom causative organisms were isolated were classified as A group. Among them were 5 patients suffered with sepsis, but the ASPC treatment eradicated all the bacteria but Salmonella java in 1 case. All of 4 patients with meningitis were cured and all causative organisms (3 cases with Haemophilus influenzae and 1 case with Gram-positive coccus) were eradicated. Cure rates were 90% for 130 patients with respiratory tract infection, 88.6% for 35 with urinary tract infection, 85.7% for 7 with skin soft tissue infection and 89.8% for all the A group patients. Meanwhile, no causative organisms were isolated from 132 patients (B group patients) but cure rate of 91.7% was obtained for this group. No statistical difference was observed between A and B groups. For all the patients (318), the cure rate was 90.6%. (2) Bacteriological effects Of 63 Gram-positive bacteria isolated as pathogens, 58 strains were eradicated. Of 117 Gram-negative bacterial, 101 were eradicated. The eradication rate on all 180 strains was 88.3%. Overall, ASPC showed excellent effects against Streptococcus. Among strains of Staphylococcus aureus, 18 of 20 strains were eradicated. Of 59 strains of H. influenzae, 52 were eradicated and 3 decreased. Among strains of Escherichia coli, 25 of 28 strains were eradicated. Of Pseudomonas aeruginosa, 2 strains were decreased and one was unchanged. (3) ASPC was effective in 93.3% of 30 patients with serious infections and 79.2% of 72 patients with underlying diseases. Cure rates for patients with and without underlying disease were significantly different statistically (chi 2: P less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)