ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

11

Electronic Resource

Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol (1992)

Nau, R. ; Prins, F.-J. ; Kolenda, H. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 181-185

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ISSN: 1432-1041

Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00278481

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12

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Formation and excretion of dipyrone metabolites in man (1992)

Zylber-Katz, E. ; Granit, L. ; Levy, M.

Springer

European journal of clinical pharmacology 42 (1992), S. 187-191

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ISSN: 1432-1041

Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00278482

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13

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Effect of salbutamol on digoxin pharmacokinetics (1992)

Edner, M. ; Jogestrand, T. ; Dahlqvist, R.

Springer

European journal of clinical pharmacology 42 (1992), S. 197-201

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ISSN: 1432-1041

Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00278484

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14

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Pharmacokinetics of nicorandil in patients with normal and impaired renal function (1992)

Molinaro, M. ; Villa, G. ; Regazzi, M. B. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 203-207

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ISSN: 1432-1041

Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00278485

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15

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The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state (1992)

Scavone, J. M. ; Greenblatt, D. J. ; Goddard, J. E. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 439-443

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ISSN: 1432-1041

Keywords: Alprazolam ; benzodiazepines ; pharmacokinetics ; pharmacodynamics ; sublingual dosage

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P〈0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng·ml−1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h·ng·ml−1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00280132

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16

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Pharmacokinetics of ethanol in plasma and whole blood: estimation of total body water by the dilution principle (1992)

Jones, A. W. ; Hahn, R. G. ; Stalberg, H. P.

Springer

European journal of clinical pharmacology 42 (1992), S. 445-448

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ISSN: 1432-1041

Keywords: Ethanol ; whole blood ; plasma ; total body water ; pharmacokinetics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of ethanol in plasma was 120 mg·dl−1 compared to 108 mg·dl−1 for whole blood. The disappearance rate of ethanol from plasma was 18.6 mg·dl−1·h−1 compared to 17.0 mg·dl−1·h−1 for the whole blood concentration-time data. The apparent volume of distribution of ethanol (Vz) was 0.54 l·kg−1 according to plasma kinetics compared to 0.59 l·kg−1 for the kinetics derived from whole blood. The mean area under the curve (AUC) was 294 mg·dl−1×h for plasma kinetics compared to 266 mg·dl−1×h for whole blood. The TBW was 40.9 l or 50.9% of body weight for the plasma concentration-time data. This agreed well with the 40.3 l or 50.1% of body weight obtained using whole blood.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00280133

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17

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High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response (1992)

Hayball, P. J. ; Cosh, D. G. ; Ahern, M. J. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 85-88

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ISSN: 1432-1041

Keywords: Methylprednisolone ; Rheumatoid arthritis ; bioavailability ; pharmacokinetics ; clinical response ; pulse steroid therapy

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu MedrolR, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00314925

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18

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Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type (1992)

Parnetti, L. ; Gaiti, A. ; Mecocci, P. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 89-93

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ISSN: 1432-1041

Keywords: Acetyl-L-carnitine ; Senile Dementia of Alzheimer Type ; pharmacokinetics ; plasma concentration ; cerebrospinal fluid concentration ; carnitine metabolism

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg·kg−1 i.v. given twice for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 2.0 g/day p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 h and 1.73 h, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00314926

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19

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Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients (1992)

Kampf, D. ; Borner, K. ; Pustelnik, A.

Springer

European journal of clinical pharmacology 42 (1992), S. 95-99

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ISSN: 1432-1041

Keywords: Ofloxacin ; Haemodialysis ; ofloxacin metabolites ; pharmacokinetics ; multiple doses ; dosage selection ; renal failure ; adverse effects

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg·1−1) and trough levels (1.6 mg·1−1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2β) and during the haemodialysis session (t1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min−1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2β of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00314927

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20

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The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis (1992)

Tracy, T. S. ; Krohn, K. ; Jones, D. R. ; [et al.]

Springer

European journal of clinical pharmacology 42 (1992), S. 121-125

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ISSN: 1432-1041

Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00278469

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