摘要:

AbstractNine healthy male volunteers took part in a crossover study to compare the pharmacokinetics of ketoprofen after administration of a single oral dose (200 mg) of ketoprofen as ‘Orudis’ capsules of encapsulated stustatained‐release pellets, ‘Oruvail’ .The mean ± standard deviation values for highest observed plasma ketoprofen concentrations were determined by high performance liquid chromatography to be 23 ± 11 μg ml−1at 0±82 ± 0±18 h after dosing with ketoprofen capsules and 3·5 ± 1·0 μg ml−1at 4·9 ± 1·0 h after dosing with sustained‐release pellets. The apparent ketoprofen elimination half‐lives after these treatments were 3·3 ± 1·2 h and 8·4 ± 3·4 h, respectively. The systemic availability of ketoprofen was essentially the same after each treatment.Administration of sustained‐release pellets (containing 200 mg ketoprofen) once every 24 h is predicated to produce similar average and markedly higher minimum plasma ketoprofen concentrations than are produced by ketoprofen capsules (100 mg) every 12h, and similar minimum plasma ketoprofen concentrations to those achieved by dosing ketoprofen capsules (50 mg) every 6 h.Once‐daily administration of a non‐steroidal anti‐inflammatory agent has an obvious therapeutic advantage over more frequent dosing. This study suggests that the sustained‐release pellet formulation described herein is a suitable formulati

ISSN:0142-2782    

DOI:10.1002/bdd.2510050302

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractA pharmacokinetic study of sachets containing nalidixic acid (0·66 g) associated with sodium citrate (3·75 g)—NSC—was carried out in 10 healthy volunteers in order to determine the influence of the urine alcalinization due to sodium citrate on the elimination of nalidixic acid (NA) and its 7‐hydroxy (HNA) and 7‐carboxy (CNA) derivatives. Urine alcaliniztion enhanced markedly the urinery excretion of HNA, but not of NA and CNA. The urinary concentrations of bacteriologically active compounds—NA + HNA—remained above five times their minimum inhibitory concentration for 10 h following each dose. After a 3‐day treatment using NSC three times daily there was no significant accumulation of NA and derivatives in the plasma and no significant change in their kinetics. Finally, from a pharmacokinetic viewpoint, the daily administration of 3 sachets of NSC each containing 0·66 g of NA seems valuable in the treatment of urinary

ISSN:0142-2782    

DOI:10.1002/bdd.2510050303

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractEffects of penicillins on the binding of phenytoin to plasma proteins were examinedin vitroandin vivo.The results fromin vitrostudies showed that the penicillins including oxacillin and dicloxacillin were effective in displacing phenytoin from its binding sites.In vivo, the total phenytoin concentration in serum decreased during penicillin administration, while the free phenytoin concentration increased. As a result, penicillins caused a significant increase in the apparent volume of distribution and in the total body clearance of phenytoin. These results can be explained on the basis of the displacement of phenytoin from its plasma protein binding site by penicillins.

ISSN:0142-2782    

DOI:10.1002/bdd.2510050304

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics and bioavailability of theophylline from a commercial oral elixir of theophylline, a rectal suppository of aminophylline, and a rectal enema of theophylline monoethanolamine was compared in six normal subjects. Using a complete crossovver design, the fasted subjects received a single dose of each dosage form. Blood and saliva samples were collected at frequent time intervals for 24 h, and the plasma assayed for theophylline by a specific thin‐layer chromatography densitometric method. No statistically significant differences existed among the three dosage forms with respect toCmaxand AUC corrected for the elimination rate constant and the dose (mg kg−1). However,tmaxwas significantly larger for the suppository. While the rate of absorption was significantly slower for the suppository, no differences in the extent of absorption existed among the three dosage forms. A one‐compartment open model with apparent first‐order absorption adequately described the plasma concentration–time data for the elixir and enema, whereas the suppository data were best fitted by a one‐compartment open model with apparent zero‐order absorption and a lag time. A rate‐limiting, concentration‐independent release of drug from the base most likely accounts for the slow absorption of theophylline from the suppository. While the saliva: plasma ratio remained fairly constant for most of the study period, the large variability found during the absorption phase following drug administration limits the usefulness of this parameter as a monitor of theophylline plas

ISSN:0142-2782    

DOI:10.1002/bdd.2510050305

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractA single dose open labelled two‐way randomized crossover study was used to assess the pharmacokinetics of diazepam from a controlled release capsule relative to standard release tablets in elderly volunteers. Eighteen volunteers received a single 15 mg controlled release capsule or a 5 mg tablet t.i.d. on one day. Diazepam plasma concentrations were determined at specific times over a 96‐h interval by an electron capture‐gas chromatographic method. Mean plateau plasma concentrations endured from 2 to 24h avoiding the peak to trough fluctuations associated with conventional t.i.d. dosing. Similar areas under the plasma concentration–time curve (AUC) values indicated equal extent of absorption between formulations and regimens. Comparing parameters in this same elderly population to a young adult population, previously administered the controlled release capsule, shows lower maximum concentrations and a longer plateau duration in the elderly volunteers. Although there is a twofold increase in the mean diazepam half‐life in the elderly when compared to young adults, the estimated apparent volume of distribution increased proportionately with half‐life to maintain a constant clearance. Thus, the total body clearance of diazepam appears to be age independent. The age‐dependent pharmacokinetics observed in this study are consistent with previously reported data involving diazepam. Overall, the controlled release capsule administered once daily mimics a t.i.d. regimen in elderl

ISSN:0142-2782    

DOI:10.1002/bdd.2510050306

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractIn a randomized three‐way crossover study, 12 healthy male volunteers were given multiple oral doses, i.e. 1·5 g b.i.d. for 7 days, of two different types of enteric‐coated acetylsalicylic acid (ASA) preparations, one being a conventional enteric‐coated tablet (ET) and the other enteric‐coated granules (EG) in a capsule; conventional ASA tablets were used as a reference. Plasma levels and excretion of salicylic acid and some of its metabolites were investigated under steady‐state conditions.Plasma salicylic acid (SA) and salicyluric acid (SUA) levels were determined using a liquid chromatographic method. Two separate analyses were done to quantitate the metabolites in urine. SA, SUA, and gentisic acid were each assayed by the method used for plasma. Total salicylate was also determined.There was no significant difference in urinary excretion of total salicylate between the three formulations. A diurnal variation in the excretion of SUA and SA in urine was found. The two enteric‐coated formulations provided significantly higher morning plasma concentrations than the conventional aspirin. The AUC was found to be significantly higher for ET than for the other two formulations. EG gave more uniform plasma levels during the studied 12‐h intervals and also less inter‐ and intra‐individual variations than ET, indicating that a b.i.d. regimen may

ISSN:0142-2782    

DOI:10.1002/bdd.2510050307

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe bioavailability and pharmacokinetics of salicylic acid (SA) were studied after single and multiple doses of a new slow‐release formulation, based on porous membrane diffusion of sodium salicylate (NaSA). A solution of NaSA and an enteric‐coated tablet of NaSA were used for comparison. Dissolution rate studies were carried out at various pH values, and both solid formulations showed pH‐dependent release rates. The entericcoated tablet released its content rapidly at intestinal pH but slowly and irregularly at gastric pH. The dissolution from the controlled‐release formulation at intestinal pH was completed after 6 h and the drug was delivered at a constant rate. At gastric pH the release rate was lower but complete release was obtained within 24h. The novel formulation appeared to offer complete bioavailability of SA and an even and sustained release of SA, allowing twice‐daily medication without increased fluctuations in SA conce

ISSN:0142-2782    

DOI:10.1002/bdd.2510050308

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractEnalapril, the ethyl ester of a potent angiotensin converting enzyme inhibitor, enalaprilat, was administered to healthy volunteers as a capsule containing 10 mg of the maleate salt, every 24 h for eight doses. Serum profiles show little accumulation of enalaprilat following eight daily doses of enalapril maleate. An average effective half‐life for accumulation of approximately 11 h was calculated from urine data. Comparison of observed 24‐h urinary recoveries of enalaprilat to predicted steady‐state recovery indicates that an ‘average’ steady state for enalaprilat is attained by the third or fourth dose of enalapril maleate. Statistical comparison of daily urinary recoveries, as well asCminvalues for enalaprilat, confirm this. Observed fluctuations in serum and urine data during apparent steady state suggest some day‐to‐day variability in the absorption of enalapril maleate and/or its hydrolysis to enalaprilat. An accumulation ratio of 1·3 for enalaprilat was calculated from the predicted steady‐state urinary recovery and observed urinary recov

ISSN:0142-2782    

DOI:10.1002/bdd.2510050309

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractA modification of the erythrocyte partitioning method for the rapid estimation of plasma‐free drug fractions (fu) is described and applied to five basic drugs. In the procedure, which uses readily available clinical laboratory equipment,fuis calculated from measurements of durg partitioning between plasma and erythrocytes, and between buffer and erythrocytes. Results obtained are compared with those from equilibrium dialysis or ultrafiltration techniques for amitriptyline, imipramine, quinidine, lidocaine, and propranolol. For each drug, the mean value offuobtained with the erythrocyte partitioning procedure was not found to be significantly different from that determined by one of the two other classical techniques. The erythrocyte partitioning method lead to reproducible (mean C.V. = 6·25) and precise values offuwhen compared to the other methods; its clinical application to lidocain gave results which agreed with those obtained by equilibrium dialys

ISSN:0142-2782    

DOI:10.1002/bdd.2510050310

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510050311

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY