摘要:

AbstractA compartmental approach for estimating the duration of the zero‐order absorption was developed. For drugs obeying one‐compartment model disposition, the estimation is based on an explicit relationship while an iterative process is required for drugs represented by two‐compartment kinetics. A method based on a double graphical plot for ascertaining absorption kinetics for drugs exhibiting one‐compartment model disposition was also de

ISSN:0142-2782    

DOI:10.1002/bdd.2510120302

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractA three‐way crossover study was performed to determine the influence of Δ9‐tetrahydro‐cannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1·5mg PCP kg−1i.v., 1·5 mg PCP kg−1i.v. with 0·4mgkg−1THC i.v., and 1·5 mg PCP kg−1i.v. with 1·25g EtOH kg−1i.v. PCP was measured in plasma samples collected for 24h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Clsvalues were significantly lower when administered with THC than when administered alone, with no significant change inVβort1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean ClsandVβwere increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP

ISSN:0142-2782    

DOI:10.1002/bdd.2510120303

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractStobadin dihydrochloride was administered p.o. to rats at a dose of 1 mg kg−1once daily for 25 consecutive days. The peak and trough concentrations of the sum of stobadin metabolites, determined from Days 6–16 of treatment, demonstrated a steady‐state. The mean daily excretion of3H‐radioactivity during this period was 43 per cent and 52 per cent of the administered dose into urine and faeces, respectively. The terminal half‐life of stobadin in plasma following a 25‐day chronic treatment was 78·3 min, which was shorter than the value of 95·3 min, determined in a single dose experiment. The data indicate that no accumulation of stobadin and of its labelled metabolites occurs in the course of repeated administration

ISSN:0142-2782    

DOI:10.1002/bdd.2510120304

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe bioavailability of potassium from orally administered potassium tartrate was evaluated in 20 normal subjects under metabolic balance conditions. Subjects were given 34 mmol potassium (5 tablets of Cal‐K®) as a divided dose on each of 2 consecutive days. Urinary excretion of potassium, as determined from 24‐h urinary collections on the 3 days preceding dosage totalled 192·6 ± 50·9 mmol (mean ± S.D.,n= 20). It increased significantly (p<0·05) to 258·7 ± 54·2 mmol for the 2 days of dosage and the following day. The difference of 66.1 mmol representing absorbed potassium was close to the 68 mmol potassium given and indicated a bioavailability of potassium in excess of 97 per cent; after correction for creatinine excretion, potassium recovery rose to 99·9 per cent. The dissolution characteristics of the Cal‐K® tablets were also determined. After dissolution in simulated gastric juice (pH 1·2), 84·4 ± 10·6 per cent (mean ± S.D., 6 experiments) was dissolved; after adjustment to pH 7·3, dissolved potassium increased to 91·3·8·5 per cent. No precipitation or residue formed as a result of the pH change. Both sets of results indicate that potassium from these potassium tartrate tablets is in a

ISSN:0142-2782    

DOI:10.1002/bdd.2510120305

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

Abstract1,2‐ and 1,3‐glyceryl dinitrates (1,2‐GDN and 1,3‐GDN) are the primary metabolites of glyceryl trinitrate, a commonly used anti‐anginal agent. The goal of this study was to examine the pharmacokinetic properties of these metabolites in rats. Sprague‐Dawley rats were infused intravenously with 0·25 or 2·0 μgmin−1of either 1,2‐ or 1,3‐GDN for 70 min, during which steady state blood concentrations were achieved. Post‐infusion blood samples were collected for 30 min. 1,2‐GDN was found to possess slightly higher clearance (32·3 vs 21·8 ml min−1kg−1) and volume of distribution (695 vs 454 ml kg−1) than 1,3‐GDN; however, the two metabolites exhibited similar mean residence times (22·0 vs 21·8 min). Upon an 8‐fold increase in the infusion rate, the pharmacokinetic parameters were not significantly altered for either 1,2‐ or 1,3‐GDN. When each GDN was co‐infused with an 8‐fold higher dose of the other GDN, there were

ISSN:0142-2782    

DOI:10.1002/bdd.2510120306

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of 2‐PAM, a component of the current nerve agent antidote therapy for U.S. military forces was compared to the pharmacokinetics of another acetylcholinesterase reactivator HI‐6. Additionally, the effects of these compounds on muscle tissue following intramuscular injection was examined. Plasma concentrations of the oximes were determined by HPLC. Plasma concentration—time profiles for both oximes fit a one‐compartment open model with first‐order absorption and elimination. The results demonstrate that the half‐time of absorption of the two oximes are nearly the same while the maximum plasma concentration of HI‐6 was significantly higher than that for 2‐PAM. Musculoirritancy was assessed on the basis of quantitative histological examinations of the injection sites and by the measurement of serum creatinine phosphokinase. Comparison of the scores from the histological sections demonstrate no difference between the two oximes. Serum creatinine phosphokinase values were elevated following injections of HI‐6, but were not consistently elevated following the

ISSN:0142-2782    

DOI:10.1002/bdd.2510120307

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe aim of this investigation was to compare two formulations of the prodrug oisaiazine (OLZ) with regard to local bioavailability of 5‐aminosalicylic acid (5‐ASA) in the colon. Since 5‐ASA can not be measured directly in the colon, the bioavailability was evaluated by studying the plasma concentration and cumulative urinary excretion (Ae) of its main metaboliteN‐acetyl‐5‐aminosalicylic acid (ac‐5‐ASA). The absorption of OLZ was also studied. A single dose of lg OLZ tablets and capsules was given to nine healthy fasting volunteers in two repeated two‐period cross‐over studies. Blood and urine samples were collected for 72 and 96h, respectively. AUC,CmaxandAedata from both studies were combined for statistical analysis. Ninety per cent confidence limits for differences in mean AUC for ac‐5‐ASA (tablet‐capsule) compared to that of capsules were ‐0·31 per cent and 30·8 per cent. This indicates bioequivalence if a more relaxed criterion than the conventional ·20 per cent is applied, which is justified in this situation. The 90 per cent confidence limits forCmaxwere ‐10·5 per cent and 36·9 per cent while for Ae the values were ‐20·5 per cent and 23·7 per cent. Within and between subject variability estimates for AUC of ac‐5‐ASA were

ISSN:0142-2782    

DOI:10.1002/bdd.2510120308

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510120309

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510120301

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY