摘要:

AbstractFour normal male volunteers participated in a study designed to examine the disposition of gold given intramuscularly as gold sodium thiomalate. Blood samples were collected for 32 days following the administration of 10 mg of gold sodium thiomalate. Plasma gold concentrations were determined by atomic absorption spectrometry. A triphasic decay pattern in plasma gold concentrations was observed. Terminal log‐linear phases corresponded to a mean disposition half‐life of 25 days. Apparent total body clearance of gold was 7·0 ± 0·6 ml kg−1day−1and the apparent volume of distribution was 0·26 ± 0·051 kg−1. These pharmacokinetic data are in contrast to previous data from other investigators who have reported half‐lives of approximately 5 days. Data from the current study provide a sound rationale for the currently used empiri

ISSN:0142-2782    

DOI:10.1002/bdd.2510050203

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractIn a random cross‐over study, eight healthy volunteers received single 10 mg doses of either nifedipine capsule (Adalat, Bayer) or nifedipine tablets (Taro) after an overnight fast. The areas under the serum concentration time curves were not significantly different (AUC0→ ∞319·8 ± 28·0 (SEM) ng ml−1h−1for capsules, 260·8 ± 15·3 ng ml−1h−1for tablets). The peak serum levels and the time of their occurrence were 162·4 ± 23·4 ng ml−1at 30 min for capsules and 43·0 ± 3·0 ng ml−1at 1–2 h for tablets, indicating that the absorption of nifedipine from the capsule is faster than from the tablet form. Clinical symptoms of vasodilation corresponded with the nifedipine peak levels. We conclude that although the bioavailability in general of the two preparations is similar, the therapeutic equivalence may differ. Depending on the therapeutic indication each

ISSN:0142-2782    

DOI:10.1002/bdd.2510050204

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractZopicloneis a new sedative showing a rapid onset of hypnotic effect and a relatively short duration of action. The goal of this study was to assess the kinetic parameters of zopiclone and its interaction with trimipramine when administered concomitantly. Ten normal subjects each received doses of zopiclone (7·5 mg), trimipramine (50 mg), and zopiclone (7·5 mg) + trimipramine (50 mg) orally at 7‐day intervals. The absorption of zopiclone was rapid, the observed plasma peak concentration and 95 per cent of all absorption occurring within one hour. The average elimination half‐life was 3·8 ± 0·2 h. The volunteers reported a bitter taste at an average of 24 min after zopiclone administration at which time concentrations in saliva were approximately 50 ng ml−1. Trimipramine decreased the relative bioavailability determined for zopiclone by 13·7 per cent, while zopiclone decreased the relative bioavailability of trimipramine by an average of 26·6 per cent, although neither of these changes was statistically significant (p>0·05); there were no substantial changes in other kinetic parameters. It is concluded that zopiclone presents advantages over some other sedative drugs as it is rapidly absorbed and eliminated. When zopiclone is administered with trimipramine, the decrease in the relative bioavailability of trimipramine may be clinicall

ISSN:0142-2782    

DOI:10.1002/bdd.2510050205

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe systemic availability of an investigational oral formulation of flurazepam was compared to that of a commercially available product whose therapeutic efficacy has been well established by usage. The experiment was designed to dissociate formula on factors from all other sources of variation including differences between subjects, sexes, sequences of administration, experimental periods, as well as sex by sequence, sex by period, and sex by formulation interactions. Systemic availability was assessed by conventional pharmacokinetic techniques.Pharmacokinetic interpretation and statistical analysis of plasma concentrations of flurazepam and its major blood metabolites namely N‐1‐hydroxyethylfurazepam and N‐1‐desalkylflurazepam as a function of time and of systemic availability indicators revealed a nearly identical biopharmaceutical behaviour for the two preparations. A significant difference could be seen in the plasma levels of N‐1‐desalkylfurazepam between male and female subjects. The results collectively indicate a very similar biopharmaceutical performance of the two oral formulations of

ISSN:0142-2782    

DOI:10.1002/bdd.2510050206

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg−1doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose‐dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration–time curves suggested that the rate of CyA absorption for all four doses was an apparent zero‐order process. Moreover, the rate of CyA absorption appeared to be dose‐dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose‐dependent characteristics in this study.Fis increased from 0·13 after the 6 mg kg−1dose to 0·22 with the 18 and 23 mg kg−1doses (p<0·05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first‐order rate constant (β) and corresponding elimination half‐life (T1/2β) of approximately 4–5 h, 0·030 h−1and 21–28 h, respectively, were similar for all CyA doses. Moreover, no difference in β was observed after oral or intravenous drug administration. Absorption lag times of 1–2 h were found. The results suggested that the apparent dose‐dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/

ISSN:0142-2782    

DOI:10.1002/bdd.2510050207

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractPlasma levels and excretion of two beta‐adrenoceptor blocking drugs3H‐exaprolol and3H‐propranolol wereobserved up to 96 h after a single i.v. administration to rats. Terminal half‐lives of 26·8 ± 9·1 h and 51·3 ± 7·5 h were found for exaprolol and propranolol, respectively. The recovery of3H radioactivity in feces following i.v. administration of the drus (34·2 ± 0·8 per cent and 12·0 ± 1·3 per cent3H of exaprolol and propranolol, respectively) is of biliary origin, as 30·7 ± 3.5 per cent and 13·4 ± 3.6 per cent3H of exaprolol and propranolol, respectively, was excreted in the bile after i.v. administration. Enterohepatic circulation of the drugs was studied using the donor‐recipient rat method. After intraduodenal administration of donor bile to the recipient rat approximately 50 per cent and 40 per cent of the biliary3H activity of exaprolol and propranolol, respectively, was re‐excreted following absorption. A formula for calculating the amount of the substance together with its metabolites excreted in the bile, urine or feces as a result of enterohepatic ci

ISSN:0142-2782    

DOI:10.1002/bdd.2510050208

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractFollowing i.v. injection of digoxin (10 μg kg−1) the ratio between digoxin concentrations in the lumen of jejunal loops perfusedin situand in plasma (L/P) of guinea pigs increased linearily with time. After 3 h, L/P was 8·7, indicating net secretion of digoxin against a concentration gradient. In quinidine treated animals (100 mg kg−1p.o., 2h before experiment) both the L/P ratio (5·7;p<0·01) and the digoxin content of jejunal tissue (– 32 per cent;p<0·01) were markedly reduced. It is suggested that quinidine reduces the extrarenal clearance of digoxin at least in part by inhibiting the intestinal secretion of this

ISSN:0142-2782    

DOI:10.1002/bdd.2510050209

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractA two‐way crossover bioavailability study of two commercial cimetidine formaulations was performed on 24 healthy male volunteers. Drug was administered after an overnight fast and plasma samples were withdrawn periodically for 12 h. Urine was collected throughout the study period. Results indicated that the two formulations were bio‐equivalent since no statistically significant difference in means was detected for any of the parameters studied. Extensive interpatient variation in cimetidine blood concentration was observed during both treatme

ISSN:0142-2782    

DOI:10.1002/bdd.2510050210

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractValpromide‐Depropylacetamide was administered to five dogs via five modes: Three oral formulations (solution, capsule, and enteric‐coated tablet), intravenous and intra‐muscular injections. No significant change in the terminal half‐life of valpromide could be observed after the various modes of administration in each dog. Valpromide was more rapidly absorbed after the administration of an oral solution than after i.m. injection. Similar data also were obtained for its metabolite—valproic acid. It was shown that valpromide in the dogs was partly biotransformed to valproic acid. The average fraction of valpromide that was transformed to valproic acid (fm) ranged from 30–35 per cent after all the oral and parenteral administrations, except for the enteric‐coated tablet, which showed a very low bioavailability

ISSN:0142-2782    

DOI:10.1002/bdd.2510050211

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe bioavailabilities of generic and reference promethazine 50 mg rectal suppositories were compared with that of 50 mg reference oral solution (24 subjects), and all three treatments were compared with a 50 mg reference i.m. injection (six subjects). Plasma samples were assayed by an HPLC method with triflupromazine as the internal standard. Both suppositories produced lower peak plasma concentrations (Cmax) and longer times to peak concentration (Tmax) than did the oral solution. There were no significant differences in the mean area under the plasma concentration–time curves (AUC) from 0 to 24 h among the three treatments. TheCmaxof the i.m. injection was significantly higher than the other three treatments, while theTmaxof the injection was significantly shorter than the reference suppository only. The mean AUC of the injection was significantly greater than the AUCs of the other three treatments. Rectal suppositories of promethazine are more slowly absorbed than oral solutions or i.m. injections; rectal suppositories and oral solutions are less bioavailable than i.m. injections. Diminished systemic bioavailability may result from extensive first‐pass hepatic metabolism that occurs after both oral and rectal dosing. There is a high degree of inter‐subject variation in the bioavailability of promethazine rectal suppositories and oral solu

ISSN:0142-2782    

DOI:10.1002/bdd.2510050212

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY