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  • 1
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of chlormethiazole following intravenous administration in the aged (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 407-415 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole pharmacokinetics ; elderly human subjects ; disposition half-life ; plasma clearance ; blood/plasma concentration ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy aged subjects were administered 1.2 g of chlormethiazole by constant-rate intravenous infusion. The disposition of the drug was found to be multi-exponential in character. Fits of plasma level-time data to two- and three-compartment open models were assessed with the aid of statistical tests. For three of the subjects the experimental data were adequately fitted to a two-compartment pharmacokinetic model, however a three-compartment model was necessary to fit the data observed for a further four subjects. An anomalous chlormethiazole plasma concentration-time curve was obtained for the remaining subject. The disposition half-life of chlormethiazole was 8.49±3.28 h and the plasma clearance was 16.14±5.00 ml/min/kg. These values were significantly different to those reported earlier for young adult subjects and the clinical implications have been discussed. The blood/plasma concentration ratio of chlormethiazole was found to be approximately one with some evidence for concentration dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563077
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of gentamicin in very low birth weight preterm infants (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 649-653 
    Details
    ISSN: 1432-1041
    Keywords: gentamicin ; preterm infants ; pharmacokinetics ; low birth weight ; dosage regimens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Low birth weight preterm infants with suspected infection were administered gentamicin intramuscularly every 18 h (2.5 mg/kg) or 24 h (3.0 mg/kg). For both dosage regimens plasma gentamicin levels were monitored during a dosage interval on three separate occasions over a 10 day period. Both regimens gave satisfactory plasma concentrations and there was no important statistically significant difference between the two. The body clearance of gentamicin correlated with gestational age (r=0.76, p〈0.01). The results indicate either regimen may be useful in the clinical situation but from a practical standpoint administration every 24 h may be easier to comply with then every 18 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542216
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  • 3
    Electronic Resource
    Electronic Resource
    Stereoselective plasma protein binding of ibuprofen enantiomers (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    Details
    ISSN: 1432-1041
    Keywords: ibuprofen ; enantiomers ; stereoselective protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(−)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(−)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558161
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  • 4
    Electronic Resource
    Electronic Resource
    Diazepam plasma binding in the perinatal period: Influence of nonesterified fatty acids (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 153-160 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; perinatal period ; plasma NEFA concentration ; regression analyses ; alpha-1-acid glycoprotein concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma binding of diazepam was determined serially in 24 women undergoing either elective induction of labour (vaginal or emergency caesarean delivery) or elective caesarean section at term and in 5 nonpregnant women requiring abdominal surgery. In the majority of pregnant patients, a marked increase in diazepam percentage free was observed during labour or prior to caesarean section, reaching a maximum, 1.6 to 3.2 fold increase at delivery or within 4 h postpartum; by the fifth day postpartum, diazepam percentage free was lower than on admission to hospital. In contrast, little change in diazepam percentage free was observed during the perisurgical period in nonpregnant patients. In parturient and surgical patients, the time courses of diazepam percentage free and plasma nonesterified fatty acid (NEFA) concentration were parallel. Bivariate regression analyses of pooled data demonstrated a strong correlation (r=0.642, p=〈0.01) between diazepam percentage free and corresponding NEFA concentration and a weaker correlation between diazepam percentage free and both albumin (r=−0.319, p〈0.02) or total protein (r=−0.438, p〈0.01). From multiple linear regression it was demonstrated that 54% of the variability in diazepam percentage free could be attributed to plasma NEFA and albumin concentrations. NEFA displacement of plasma bound diazepam was substantiated using crystalline human serum albumin. An approximate 65% increase in plasma α1acid glycoprotein levels was observed posttrauma in both parturient and surgical patients but was unrelated to diazepam binding events. A relationship between diazepam plasma binding changes and concurrently altered disposition of diazepam during parturition is postulated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542461
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of betamethasone in healthy adults after intravenous administration (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 643-650 
    Details
    ISSN: 1432-1041
    Keywords: betamethasone ; pharmacokinetics ; cortisol ; high-performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of betamethasone and its phosphate ester are described in 8 healthy adults after i. v. bolus injection of 10.6 mg betamethasone phosphate. Both compounds were measured by high-performance liquid chromatography with ultraviolet detection using sample handling methods which prevented hydrolysis of the ester in vitro. Betamethasone phosphate disappeared rapidly from plasma (mean half-life=4.7 min) as betamethasone levels rose. Betamethasone plasma levels reached a peak 10–36 min after administration of the phosphate before declining in a biexponential manner. The terminal slow disposition phase had a mean half-life of 6.5 h. Only about 5% of the dose was recovered from urine as betamethasone, indicating extensive extrarenal clearance of betamethasone. Protein binding and blood/plasma concentration ratio were also determined. In comparison with its stereoisomer, dexamethasone, betamethasone is also cleared mainly by metabolism but has a lower plasma clearance, is less plasma bound, has a higher blood/plasma concentration ratio, and a higher volume of distribution. Endogenous cortisol levels were measured in the subjects who received betamethasone phosphate and in a matched control group of 4 subjects who did not. Betamethasone abolished the normal episodic secretion of cortisol and rapidly reduced its plasma concentration to a basal level. Cortisol plasma levels were not restored at 24 h but had returned to normal by 48 h after dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542353
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cimetidine in critically ill patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 341-346 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; pharmacokinetics ; critically ill patients ; intravenous administration ; dose individualization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15–35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30–50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p〈0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548765
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  • 7
    Electronic Resource
    Electronic Resource
    Plasma level of chlormethiazole and two metabolites after oral administration to young and aged human subjects (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 137-145 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; metabolites ; oral administration ; young and elderly human subjects ; quantitative gas chromatographymass spectrometry ; whole blood distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of chlormethiazole and two of its metabolites has been measured in three young and three aged human subjects following administration of a single oral dose of chlormethiazole. A sensitive analytical method based on gas chromatography-mass spectrometry using the selective ion monitoring mode of operation was developed to permit quantitation of the plasma levels. The time course of the plasma concentration of chlormethiazole and metabolites showed wide inter-subject variation, particularly between the young and elderly subjects. Absorption of chlormethiazole was rapid in the subjects of both groups as assessed by the time taken to reach the peak plasma concentration. The mean peak plasma level of chlormethiazole was more than five times greater in the elderly (2.90±1.56 µg/ml) than in the young (0.55±0.58 µg/ml) subjects. The plasma level of chlormethiazole was consistently higher in the aged subjects and this was reflected by the larger area under the plasma curve in aged (7.62±5.37 µg.h/ml) than in young (0.94±0.66 µg.h/ml) individuals. Decreased pre-systemic elimination by the liver has been suggested as an important factor contributing to the higher plasma level in the elderly. Estimates of absolute systemic availability, calculated by reference to previous intravenous studies, were greater for the elderly subjects. The distribution of chlormethiazole in whole blood from six young and six elderly human subjects was investigated in vitro. The unbound fraction of chlormethiazole in plasma increased significantly from 0.308±0.035 in young subjects to 0.403±0.067 in the elderly. Distribution of the drug in whole blood was different for the two age groups; the fraction of drug distributed to plasma water was significantly greater and the fraction in blood cells was significantly less in the aged.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645135
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  • 8
    Electronic Resource
    Electronic Resource
    The placental transfer of betamethasone (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 245-247 
    Details
    ISSN: 1432-1041
    Keywords: betamethasone ; pregnancy ; placental transfer ; plasma concentrations ; HPLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of beta-methasone in a maternal peripheral vein (mv) and in the umbilical vein (uv) were measured at delivery in eleven patients after the administration of beta-methasone phosphate equivalent to 8 mg betamethasone. Betamethasone concentrations were measured in plasma using a specific and sensitive HPLC assay. The time interval between the last dose and delivery ranged from 56 min to 800 min and over this time period the mean plasma concentration ratioCuv/Cmv was 0.28±0.04 (SD) and exhibited no time dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563006
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  • 9
    Electronic Resource
    Electronic Resource
    Sorption of chlormethiazole by intravenous infusion giving sets (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 333-338 
    Details
    ISSN: 1432-1041
    Keywords: chlormethiazole ; sorption by infusion ; giving sets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The sorption of chlormethiazole by intravenous infusion giving sets was investigated. Average recoveries of chlormethiazole following 500 ml infusions were 78.5%, 82.2% and 71.2% for the IVAC Volume Infusion Set, Travenol Code AHC 2890 Blood Administration Set and the McGaw Metriset, respectively. The effluent concentration-time profile using set up procedures and infusion rates similar to those used clinically were followed. When compared to solutions flowing at an infusion rate of 75 and 150 ml/h, loss of chlormethiazole from solutions standing static in the influsion sets was higher while that of solutions flowing at a high rate of 999 ml/h was lower. The clinical and pharmacokinetic significance of these phenomena are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561391
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  • 10
    Electronic Resource
    Electronic Resource
    Differential transplacental binding of diazepam: Causes and implications (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 595-601 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; fatty acid binding ; matched maternal and foetal plasma ; plasma NEFA concentration ; plasma bilirubin ; plasma albumins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diazepam plasma binding was determined in 17 matched pairs of maternal and foetal plasma, collected at delivery. Diazepam % free was higher (p〈0.001) in maternal (mean 3.24%) than in either umbilical venous (mean 1.50%) or umbilical arterial (mean 1.24%) plasma. The data from in vitro dialysis studies were consistent with the reported higher diazepam concentrations in infants than in mothers at delivery. Plasma nonesterified fatty acids (NEFA) concentrations were higher (p〈0.001) in maternal (x = 643 μM) than in matched umbilical venous plasma (x = 211 μM) and there was a significant correlation (p〈0.01) between diazepam % free and corresponding plasma NEFA concentration for pooled data (r=0.871, n=34). Multiple and partial regression analysis indicates that transplacental differences in albumin, bilirubin and total protein concentrations made a minimal contribution to diazepam binding differences between mother and foetus and that approximately 76% of the variability in diazepam % free was accounted for by plasma NEFA concentration. The binding of diazepam to human serum albumin (HSA) was markedly perturbed by the presence of NEFA but not by bilirubin and there was no apparent cooperativity between bilirubin and NEFA on diazepam-HSA binding. Moreover, our findings provide further evidence that substantial differences in binding affinities exist between foetal and maternal plasma albumins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542207
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