摘要:

The pharmacokinetics of cefpodoxime were evaluated in 30 paediatric patients (12 females and 18 males, 1.0 to 17.2 years of age) with normal renal and hepatic function following a single oral dose (4.5 ± 0.8 mg/kg, range 2.7 to 5.0 mg/kg) of cefpodoxime proxetil. Cefpodoxime was quantitated from repeated blood and urine samples obtained over a 12-hour postdose period by HPLC. Apparent peak plasma cefpodoxime concentrations ranged between 0.8 and 3.4 mg/L (2.2 ± 0.6 mg/L), and were observed between 2 and 4 hours following drug administration. A lag-time (0.46 ± 0.26 hours, range 0 to 1.1 hours) was evident in 27 of 29 subjects. Mean (± SD) values for the absorption rate constant (Ka), absorption half-life (t½Ka), and time for 90% absorption were 0.84 ± 0.44h−1, 0.82h and 3.6 ± 0.6h, respectively. Values for the elimination rate constant (Kel), apparent total plasma clearance (CL/F) and apparent steady-state volume of distribution (Vdss/F) were 0.41 ± 0.06h−1, 0.42 ± 0.15 L/h/kg (range 0.16 to 0.93 L/h/kg) and 1.08 ± 0.49 L/kg (range 0.47 to 2.9 L/kg), respectively. The mean renal clearance (CLR) for cefpodoxime in 18 subjects was 0.11 L/h/kg and represented 26% of the mean CL/F. Inverse linear correlations were found between patient age and both CL/F (r = 0.67, p < 0.001) and Vdss/F (r = 0.55, p < 0.01), thus demonstrating developmental dependence for these 2 parameters. Accordingly, when CL/F, Vdss/F and Kawere compared between patients less than 5 years of age and those aged 5 years or more, significant differences were found (i.e. 0.57 ± 0.16vs0.36 ± 0.1 L/h/kg for CL/F, 1.52 ± 0.56vs0.89 ± 0.3 L/kg for Vdss/F and 1.12 ± 0.77vs0.73 ± 0.18h−1for Ka); the larger values for each parameter being seen in the youngest age group. These data support a developmental dependence in the disposition of cefpodoxime in paediatric patients following the administration of the prodrug ester, cefpodoxime proxetil.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The pharmacokinetics of perrimustine and cystemustine, 2 novel 2-chloroethylnitrosoureas (CENUs), were investigated in patients with various cancer diseases. The unique protocol followed in this study consisted of a 15-minute intravenous (IV) perfusion of a 45 mg/m2dose of perrimustine every 4 weeks and a 60 or 90 mg/m2dose of cystemustine every 2 weeks. A sensitive and specific method was developed using solid phase extraction and HPLC analysis, which allowed measurement of the drug concentration levels until at least 3 hours after the beginning of administration of the injection. The rate of disappearance of the 2 drugs from the blood was fitted to either a monoexponential or a biexponential model. When detected, the half-lives of the distribution phase were less than 10 minutes. Regardless of the pharmacokinetic model used, the elimination half-lives were about 50 minutes. The interindividual variations of the pharmacokinetic parameters, as reflected by the variation coefficients (10 to 47%), were lower than those reported in the literature for this class of unstable anticancer drugs. The procedure described here allows one to safely conduct perrimustine and cystemustine pharmacokinetic studies with the purpose of further investigation in a greater number of patients to determine whether any correlation exists between pharmacokinetics, efficacy and/or toxicity.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

This study set out to compare and evaluate the efficacy, over a 6-month period, of smoking cessation programmes involving transdermal nicotine patches in two different Australian settings: a workplace programme and a general medical practice programme.Other objectives were: (a) to compare the success of smokers of high versus low nicotine dependence; (b) to assess whether early morning craving is more severe than cravings at other times of the day during treatment; and (c) to monitor adverse events experienced throughout the nicotine treatment phase.The study was an open uncontrolled multicentre trial, that took place in: (a) 15 general practices in the Queensland Gold Coast region; and (b) workplace settings within the Victorian branch of the Commonwealth Department of Veterans' Affairs and the Heidelberg Repatriation Hospital in Heidelberg, Victoria.The participants included: (a) general practice setting: 121 participants recruited from the general practitioners' patient pool in the Gold Coast region; (b) workplace setting: 85 participants recruited from employees, and their partners.Continuous abstinence [defined as the participant attending each session, reporting abstinence at each session, and having a carbon monoxide (CO) concentration of ≤ 8 ppm at each session] was achieved in 21% of participants at 3 months, falling to 17% at 6 months, in the general practice programme, and 28% of participants at 3 months, falling to 22% at 6 months, in the workplace programme. Point abstinence (defined as reporting abstinence at the 3- and 6-month follow-ups and having a CO of ≤ 8 ppm) was achieved in 32% (at 3 months) and 27% (at 6 months) of participants in the general practice programme and in 44% of participants (at 3 months) and 33% (at 6 months) in the workplace programme. On a 5-point scale of severity (0 to 4), cravings and other withdrawal symptoms were reported as slight (1) to mild (2) on average in the first week of the study and declined throughout the study period. During the waking hours, cigarette craving was reported to be lowest in the morning. Transdermal nicotine therapy was well tolerated.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The single dose pharmacokinetics of temocapril, a novel prodrug type angiotensin converting enzyme (ACE) inhibitor with preferential biliary excretion, were evaluated in 6 patients maintained on haemodialysis and in 1 patient on continuous ambulatory peritoneal dialysis (CAPD). In a crossover design, each haemodialysis patient received a single oral dose of temocapril 1mg after breakfast on two occasions, on dialysis and nondialysis days, at an interval of 1 week. The CAPD patient received a single oral dose of temocapril 1mg. Plasma concentrations of temocapril and its active metabolite (diacid) and ACE activity were determined after drug administration. Area under the plasma concentration-time curves (AUC) in haemodialysis patients on the nondialysis day were significantly greater than those in patients with normal renal function who were used as a reference (p < 0.01). Other pharmacokinetic parameters such as maximum plasma drug concentration (Cmax), biological half-life (t½) and time to reach Cmax(tmax) were not significantly different between the 2 groups. 24 hours after administration, the ACE inhibitions in haemodialysis patients were significantly higher than those in patients with normal renal function. There were no other significant differences between the 2 groups. The peak level of diacid (Cmax) in haemodialysis patients on the nondialysis day was significantly greater than that on the dialysis day (p < 0.05). Other pharmacokinetic parameters such as AUC, t½and tmaxwere not significantly different between these 2 days. These parameters in the CAPD patient were similar to those in the haemodialysis patients on dialysis day. The results suggest that the elimination route of temocapril is mainly via the biliary route, but is partially a route permeated through a dialyser membrane or peritoneal membrane. It is suggested that temocapril is preferable to ACE inhibitors with renal elimination in the treatment of patients with hypertension undergoing dialysis.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Three single dose open-label crossover studies in healthy adult males (n = 24 or 30) evaluated the sustained release characteristics, bioavailability, influence of food, linearity of kinetics and metabolite to morphine molar ratios of KapanolTMcompared with oral morphine solution and MST Continus®tablets. Drugs were administered 7 days apart following either a 12-hour fast or a standard high-fat meal. All blood samples (36 or 48 hours) were analysed for morphine (high-performance liquid chromatography [HPLC]-electrochemical detection) and a subset was analysed for morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) [HPLC-ultraviolet]. KapanolTM(fasted and fed) had a pharmacokinetic profile consistent with a sustained release of morphine (M) and there was no evidence of dose-dumping. No significant differences occurred in the dose-adjusted area under the plasma concentration-time curve (AUC) values for KapanolTM(50mg) [fasted and fed] and solution (25mg) [fasted]. The bioavailability of KapanolTMrelative to solution was 107 and 111% on fasting and fed states, respectively. The AUC molar ratios of M-3-G and M-6-G to M were not significantly different for KapanolTMand solution (mean molar ratio M : M-6-G : M-3-G = 1 : 7 : 30). KapanolTMdisplayed linear pharmacokinetics over the dose range of 30 to 100mg. KapanolTM50mg had a slower absorption rate and a longer duration over which plasma morphine levels were equal to or above 75% peak concentration than MST Continus®60mg, while no differences occurred in the extent of morphine absorption from the 2 formulations. In conclusion, the pharmacokinetics of KapanolTMare consistent with a sustained-release formulation suitable for at least 12-hourly dose administration. The slow, sustained absorption of morphine from KapanolTMmay provide clinical advantages over other morphine preparations.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

1-Acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione (APTD) has hypolipidaemic, anti-inflammatory, analgesic, antineoplastic, and aldose reductase inhibitory activities in animals. Disposition studies using pooled plasma and urine samples showed that [1-14C-acetyl]-1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione (14C-APTD) had a maximum half-life of 20 hours. Urinary excretion accounted for less than 3% of the radioactivity elimination, while faecal excretion may account for up to 45% of the total elimination. In a 96-hour tissue distribution study, there was no sequestering of14C-APTD in any of the organs.14C-APTD demonstrated significant aqueous partitioning, and almost no binding to bovine serum albumin. In L1210tumour cells,14C-APTD was bound to DNA and RNA, and there was no binding to intracellular protein.14C-APTD underwent significant metabolism in mice. One metabolite excreted in urine was identified; two other possible metabolites were proposed.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS