Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • pharmacokinetics  (12)
  • benzodiazepine  (2)
  • aged patients  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 381-388 
    ISSN: 1432-1041
    Keywords: midazolam ; hypnotic drug ; benzodiazepine ; pharmacokinetics ; aged patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg−1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg−1h−1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg−1) and the young subjects studied previously (1.09±0.58 l kg−1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44–50 µg l−1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 271-278 
    ISSN: 1432-1041
    Keywords: midazolam ; benzodiazepine ; pharmacokinetics ; gas-liquid chromatography ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Midazolam, a new water-soluble benzodiazepine, was administered as: i) 5 mg intravenously, ii) a 10-mg oral solution and iii) a 10-mg oral tablet, to six volunteers whose informed consent had been obtained. Midazolam plasma concentrations were measured using an electron-capture gas-liquid chromatographic assay. After 5-mg intravenous midazolam, subjects fell asleep within 1–2 min and continued to sleep for an average of 1.33 h. After oral midazolam intake (solution or tablets), drowsiness appeared after a average of 0.38 h (range 0.25–0.55 h) and sleep continued for an average of 1.17 h. The time to reach peak plasma midazolam concentration after the 10-mg solution dose (0.37±0.45 h) did not differe significantly (‘t’=2.04, df=10,p〉0.05) from the time to reach peak plasma midazolam level after the 10-mg tablet dose (0.74±0.45 h). The terminal half-life, (t1/2), of midazolam in plasma was 1.77±0.83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations. The mean total clearance (Cl), of midazolam after 5-mg intravenous administration was 0.383±0.094 l·kg−1·h−1. The first pass effect, F, determined experimentally (0.36±0.09) indicated the substantial first pass metabolism of midazolam. The percentage of the midazolam dose excreted unchanged in urine in four subjects during the 0-8-h urine collection interval was very small (0.011%–0.028%).
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 65-67 
    ISSN: 1432-1041
    Keywords: tizanidine ; pharmacokinetics ; spasticity ; multiple sclerosis ; haematological parameters ; electromyogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of plasma concentrations of the antispasticity agent tizanidine were measured by a specific radioimmune-assay in six adults who had severe spasticity due to multiple sclerosis. The drug was given as a single oral 4 mg dose to each subject. The drug had a mean absorption half-life of 0.30±0.155 h following a mean lagtime of 0.361±0.118 h, and a mean terminal elimination half-life of 4.16±2.06 h. Only 2.65±0.82% of the dose was excreted unchanged in urine in 2 h. Calculated values of clearance and apparent volume of distribution were almost certainly overestimates as it seems probable that the orally-administered drug undergoes significant presystemic elimination (its bioavailability was not determined in the investigation here reported). Relief of spasticity, from the dosage used, was relatively slight and appeared greatest at the time of peak plasma levels of the drug.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 177-182 
    ISSN: 1432-1041
    Keywords: glibenclamide ; bioavailability ; pharmacokinetics ; dissolution ; hypoglycaemia ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been carried out investigating four different marketed oral preparations of glibenclamide, correlating the effectiveness of the drug in these preparations in lowering plasma glucose concentrations with (i) the in vitro dissolution of the drug, measured by the British Pharmacopoeal and Desaga methods, and (ii) the in vivo bioavailability, assessed in 12 healthy human volunteers. The two dissolution methods yielded different rank orders of ease of dissolution of the drug from the various preparations; the findings of neither dissolution method correlated adequately with the results of the in vivo bioavailability studies, which correctly predicted the abilities of the preparations to reduce plasma glucose concentrations. Relative to an oral glibenclamide solution the bioavailabilities of the drug from three tablet preparations were 0.69, 0.49 and 0.24. The mean elimination half-life of the drug was 1.5 h and assuming complete bioavailability of the drug from oral solution the mean systemic clearance was 0.095 l kg−1h−1, and the mean apparent volume of distribution was 0.20 l kg−1. It is concluded that it may be unsafe to use in vitro dissolution data as a basis for assessing the bioequivalences of different glibenclamide preparations intended for oral use.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 777-785 
    ISSN: 1432-1041
    Keywords: aspirin ; migraine ; salicylic acid ; metoclopramide ; drug absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of aspirin (ASA) in acute migraine attacks, and the influence of metoclopramide on ASA disposition, were studied in 32 attacks in 30 patients. An intergroup comparison was made between normal volunteers, and the migraineurs, who were assigned at random to one of three treatment groups: a) oral ASA only (900 mg); b) 10 mg oral metoclopramide + oral ASA 900 mg; c) 10 mg i. m. metoclopramide + oral ASA 900 mg. Plasma ASA and SA levels were measured serially over 2 h, and the resultant data evaluated pharmacokinetically. Metoclopramide plasma levels were also determined over 2 h, and the results compared with a second group of normal volunteers. The rates of oral ASA absorption and elimination were unaffected by migraine. Mean absorption rate constants of 14.15±9.48 h−1 (normals), 7.91±3.42 h−1 (ASA only), 6.74±3.26 h−1 (ASA + oral metoclopramide) and 8.12±2.82 h−1 (ASA + i. m. metoclopramide) were calculated. Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1, and did not differ significantly between controls and migrainous patients. Values for absorption lag time, however, were higher in migraine patients treated with ASA alone than in any other group. The amount of ASA absorbed unhydrolysed was also lower in this group. SA levels appeared unaffected either by the migraine attack, or by metoclopramide administration, over the period of study. Metoclopramide plasma levels were significantly lower during migraine attacks, and the amount of drug absorbed up to 2 h from dosing was also reduced, as compared with non-migrainous subjects. It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites, probably as a result of gastric stasis, and may have decreased the amount of ASA absorbed. The prior administration of metoclopramide, either orally or intramuscularly, reduced the absorption lag time, and thus promoted the early absorption of ASA, probably by restoring alimentary tract motility.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 451-456 
    ISSN: 1432-1041
    Keywords: Bioavailability ; carbamazepine ; elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following values were obtained for various pharmacokinetic parameters:k abs =0.176±0.209 h−1;k=0.0203±0.0055 h−1; T1/2=37.5±13.1 h; VD=0.825±0.1041 · kg−1; Clearance=0.0163±0.0061 l · kg−1. The elimination rate constant showed a statistically significant increase with increasing drug dose. This may help explain the clinical observation that the rate of rise of steady state plasma carbamazepine concentrations tends to decrease with dose increase in patients taking carbamazepine alone.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...