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Biomedical subjects

D R Guay

Publications and source records attributed to D R Guay.

At least 73 records · Page 4Linked to original sources
PubMed1987

Pharmacokinetics of ciprofloxacin in acutely ill and convalescent elderly patients.

The pharmacokinetics of ciprofloxacin were evaluated in 13 elderly patients with serious infections who were receiving 750 mg orally every 12 hours. The acute evaluations were performed within 24 hours of admission (n = 13), whereas the convalescent evaluations were performed at the end of therapy (n = 7). Serum and urine concentrations of ciprofloxacin were measured using high-performance liquid chromatography. Peak serum concentration (Cmax), terminal elimination half-life (t1/2 beta), apparent total body clearance (CL/f), and apparent volume of distribution (Vd/f) of ciprofloxacin were 5.97 +/- 2.95 mg/liter, 5.31 +/- 2.00 hours, 8.12 +/- 3.83 ml/kg/minute, and 3.63 +/- 1.91 liters/kg during the period of acute illness. Cmax and Vd/f values were moderately increased during the convalescent phase (8.56 +/- 3.43 mg/liter versus 5.87 +/- 2.25 mg/liter, p = 0.138, and 5.95 +/- 3.23 liters/kg versus 3.46 +/- 1.40 liters/kg, 0.05 less than p less than 0.1). The CL/f and t1/2 beta (four to 12 hours) values, however, were not significantly altered. The observed pharmacokinetic characteristics, which are consistent with those derived from single-dose studies in healthy elderly subjects, are markedly different from previous observations in young adult volunteers. However, acute illness does not alter the pharmacokinetics of ciprofloxacin in the elderly. Dosage alterations because of the presence of acute illness in the elderly do not appear to be warranted.

Administration, Oral↗
PubMed1987

Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers.

The pharmacokinetics of codeine, codeine glucuronide, morphine, and morphine glucuronide were assessed after single- (60 mg) and multiple-dose (60 mg every six hours for nine doses) oral administration of codeine sulfate to six normal volunteers. Multiple blood and urine samples were collected after administration of the single- and last multiple-oral doses. Drug concentrations were analyzed using radioimmunoassay techniques. No significant alterations in codeine pharmacokinetics were noted after multiple-dose oral administration. However, accumulation of morphine during multiple dosing was significant (AUC24 = 102 +/- 33 ng/mL/hr after single dose versus 212 +/- 118 ng/mL/hr after the last multiple dose). Peak concentration and AUC24 data for morphine glucuronide indicated that significant accumulation of this compound occurs upon multiple-dose administration. These data indicate that morphine and morphine glucuronide serum concentrations are significantly increased during chronic oral codeine therapy and suggest that morphine, and perhaps morphine glucuronide, contribute significantly to the analgesic activity of chronic oral codeine therapy.

Adult↗
PubMed1987

Influence of gender on the disposition of cefotaxime and desacetylcefotaxime.

The pharmacokinetics of cefotaxime and desacetylcefotaxime were evaluated in 11 female and 13 male subjects with end-stage renal disease. Subjects received single 1- or 2-g intravenous doses of cefotaxime sodium. Serum, urine, and dialysate concentrations of cefotaxime and desacetylcefotaxime were determined using high performance liquid chromatography. The results indicate that gender has no clinically significant influence on the disposition of cefotaxime or its active metabolite desacetylcefotaxime.

Cefotaxime↗
PubMed1986

Pharmacokinetics of cefixime (CL 284,635; FK 027) in healthy subjects and patients with renal insufficiency.

The pharmacokinetics of the extended-half-life, broad-spectrum oral cephalosporin cefixime (CL 284,635; FK 027) were studied in 7 healthy volunteers and 35 patients with various degrees of renal insufficiency, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. Apparent total body, renal, and apparent nondialysis-nonrenal clearances and protein binding declined and elimination half-life increased with decreasing creatinine clearance. All of these alterations became statistically significant as the creatinine clearance fell below 20 ml/min per 1.73 m2. Cefixime concentrations in urine exceeded the MICs for most urinary tract pathogens for up to 24 h postdose, even in patients with severe renal insufficiency. CAPD removed an insignificant fraction of cefixime body burden over the 72-h study period (1.57 +/- 0.60% [mean +/- the standard error of the mean]). Area under the curve data suggested that hemodialysis similarly removed an insignificant fraction of the cefixime body burden. Volume of distribution at steady state was not altered significantly by renal insufficiency. It is recommended that standard doses of cefixime be administered at extended intervals, especially in patients with creatinine clearances less than 20 ml/min per 1.73 m2. In addition, supplemental doses are not necessary during CAPD and at the end of hemodialysis.

Adult↗
PubMed1985

Analysis of meperidine and normeperidine in serum and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the simultaneous analysis of meperidine and normeperidine in serum and urine. A 1-ml sample aliquot is extracted into hexane, then back-extracted into a small volume of dilute acid which is injected onto a cyanopropyl analytical column. Absorbance of the column effluent is monitored at 205 nm. Two internal standards are employed, diphenhydramine for meperidine and nordiphenhydramine for normeperidine. Chromatography of the four compounds takes 4 min. Serum concentration--time curves of meperidine and normeperidine are presented for eight healthy subjects following single 70-mg bolus injections of meperidine.

Adult↗
PubMed1985

Vancomycin-induced neutropenia.

Although rare, neutropenia associated with long-term vancomycin therapy may occur. A 67-year-old woman with cellulitis and sepsis caused by Staphylococcus aureus was treated initially with cefazolin. Despite in-vitro susceptibility of the organism to this drug, the patient remained febrile, and therapy was changed to vancomycin. On day 17 of therapy with this medication neutropenia was noted; it progressed over the next 3 days, and therapy with the drug was stopped. A rise in the neutrophil count occurred within 5 days of discontinuation. Periodic monitoring of the leukocyte count during longterm vancomycin therapy is recommended.

Aged↗
PubMed1985

Ranitidine does not alter pethidine disposition in man.

The effect of concurrent ranitidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (19-33 years). The subjects received 70 mg i.v. pethidine HCl doses before and during ranitidine treatment (150 mg p.o. twice daily). Ranitidine therapy was not associated with significant alterations in pethidine elimination rate constant, volume of distribution at steady state, total body clearance, and 24 h urinary excretion. No alteration in pethidine oxidation to norpethidine was noted, as suggested by nonsignificant changes in lag time to appearance of quantifiable norpethidine in serum, time to peak concentration, peak concentration, area under the curve from time 0.24 h, and 24 h urinary excretion. It would appear that, unlike cimetidine, ranitidine does not interact pharmacokinetically with pethidine. Further studies are necessary to evaluate the potential clinical advantages of ranitidine vs cimetidine therapy in patients also receiving pethidine.

Adult↗
PubMed1984

Isothermal gas chromatographic analysis of diphenhydramine after direct injection onto a fused-silica capillary column.

The packed column injector of a gas chromatograph was modified to accommodate direct injection by syringe onto a wide-bore fused-silica capillary column. No changes were made to the nitrogen-phosphorus detector. The resultant configuration combines fast separations with precise quantitations. The analysis of diphenhydramine in serum is presented as an application. Chromatographic separation of diphenhydramine and orphenadrine (internal standard) from caffeine and other endogenous material takes 2 min. Serum diphenhydramine concentrations are presented for six volunteers following a 50-mg oral dose.

Caffeine↗
PubMed1984

Cimetidine alters pethidine disposition in man.

The effect of concurrent cimetidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (18-31 years). The subjects received 70 mg i.v. pethidine HCl doses before and during cimetidine treatment (1200 mg/day p.o.). During cimetidine treatment, pethidine total body clearance (CL) decreased by 22% (0.611 +/- 0.101 [mean +/- s.d.] to 0.474 +/- 0.098 1 kg-1 h, P less than 0.05) and pethidine volume of distribution at steady state (Vss) decreased by 13% (4.79 +/- 0.82 to 4.16 +/- 0.75 l/kg, P less than 0.05). A cimetidine-induced reduction in pethidine oxidation to norpethidine was suggested by a 23% reduction in norpethidine area under the curve from 0 to 24 h (472 +/- 93 to 362 +/- 38 ng ml-1 h, P less than 0.05) and a 29% reduction in peak norpethidine concentration (26.7 +/- 5.3 to 18.9 +/- 1.9 ng/ml, P less than 0.05). There were no significant linear correlations of serum trough cimetidine concentration with percentage reductions in pethidine CL, pethidine Vss, norpethidine AUC (24), or norpethidine peak concentrations. It would appear that the cimetidine-pethidine kinetic interaction may be of sufficient magnitude to be clinically significant. Caution is advised when patients are treated concurrently with these two agents.

Adolescent↗
PubMed1984

Pharmacokinetics of metronidazole in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of metronidazole, its biologically active alcohol metabolite, and its inactive acid metabolite were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis and five patients undergoing hemodialysis. The latter were studied on off-dialysis days as a control group. Peritoneal dialysis caused insignificant changes in the apparent volume of distribution, elimination half-life, and total body clearance of metronidazole. Peritoneal dialysis clearance (4.49 +/- 0.88 ml/kg per h [mean +/- standard deviation]) accounted for only 8.9% of total body clearance (50.17 +/- 18.64 ml/kg per h). Analysis of the 24-h area under the serum concentration versus time curves and peritoneal dialysis clearance data for the two metabolites suggested a similar insignificant effect of peritoneal dialysis on their elimination. Metronidazole dialysate concentrations in the first 6-h exchange ranged from 7.6 to 11.7 micrograms/ml. This would suggest that cumulative penetration of metronidazole from the systemic circulation into the peritoneal cavity with dosing every 8 h should lead to adequate concentrations for the treatment of anaerobic peritonitis. For the treatment of systemic anaerobic infections, it would appear at present that metronidazole dosage adjustments are not necessary in patients undergoing continuous ambulatory peritoneal dialysis. The potential for metabolite accumulation was noted in this study. If further studies confirm that excessive serum metabolite concentrations are toxic, dosage reduction in this group of patients may be warranted.

Adult↗
PubMed1984

Heparin-induced thrombocytopenia--association with a platelet aggregating factor and cross-sensitivity to bovine and porcine heparin.

Heparin-induced thrombocytopenia is an infrequently suspected adverse drug reaction since its sequelae often mimic the underlying condition for which the drug is being used. A concomitant decline in platelet count and increase in heparin requirements should alert the clinician to the possible presence of this disorder. A 36-year-old black male developed severe thrombocytopenia with thrombosis while being treated with porcine intestinal mucosal heparin. Platelet counts returned to near-normal levels upon discontinuation of heparin, but quickly dropped again upon resuming treatment with bovine lung heparin. The patient subsequently was treated with warfarin and dipyridamole, with no further complications. Treatment of delayed-onset severe heparin-induced thrombocytopenia consists of stopping the heparin and substituting antiplatelet agents and oral anticoagulants when continued inhibition of coagulation is required.

Adult↗
PubMed1984

Activated charcoal adsorption of diphenhydramine.

The adsorption of the antihistamine diphenhydramine (D) by activated charcoal (AC) was assessed in vitro and in vivo in six healthy volunteers in order to assess the utility of AC as an adjunct in the treatment of antihistamine overdose. Results of greater than 85% adsorption with AC:D weight ratios of 10:1 or greater in the in vitro studies led to a three-way crossover trial in six volunteers. Fifty mg D was administered alone (control), with 50 g AC within 5 minutes of D (D + C5) and with 50 g AC 60 minutes after D (D + C60). Mean reductions in peak serum D concentrations of 94.8% (D + C5) and 12.3% (D + C60), AUC 0-24 h of 96.9% (D + C5) and 20.4% (D + C60), and AUC 0-omega of greater than 90% (D + C5) and 24.0% (D + C60) were noted, although only the comparison of D with D + C5 reached statistical significance due to wide interpatient variation. A positive correlation of time to peak concentration of drug in serum in the control group with percentage reduction in AUC in the D + C60 group further indicate the potential for positive therapeutic benefit of AC in antihistamine overdose. This is because lag time and time to peak concentration may be excessively prolonged in overdose due to anticholinergic-induced alterations in G.I. motility. Maximal and multiple doses of AC are recommended for adjunctive treatment of antihistamine overdose.

Adsorption↗
PubMed1983

Netilmicin (Netromycin, Schering-Plough).

Netilmicin sulfate, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside recently released for use in Canada and not yet released in the U.S. Its place in therapeutics, compared with gentamicin (G), tobramycin (T), and amikacin (A), is not yet established. Preliminary work in animals has suggested a lower incidence of nephrotoxicity and ototoxicity than with other aminoglycosides, and in vitro work has suggested some activity against G/T-resistant organisms. However, netilmicin appears to be virtually identical to G,T, and A in antimicrobial spectrum (except for its poorer activity against P. aeruginosa), human toxicity, and clinical use. For G/T-resistant organisms, amikacin is still the aminoglycoside of choice. In summary, netilmicin has not been demonstrated to have significant advantages over other aminoglycosides (G,T,A), and it is more expensive; thus, its potential value is limited.

Animals↗
PubMed1983

Toxicological findings in a death resulting from the ingestion of trimipramine.

A fatality following ingestion of the tricyclic antidepressant trimipramine is presented. Whole blood concentrations of trimipramine and its metabolite N-desmethyltrimipramine were measured by gas-liquid chromatography and found to be 400 and 1130 ng/mL, respectively. These findings are compared to those of previous unpublished trimipramine fatalities and fatalities caused by other tricyclic antidepressants.

Chromatography, Gas↗