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D R Guay

Publications and source records attributed to D R Guay.

At least 37 records · Page 2Linked to original sources
PubMed1994

Evaluation of two intravenous single-bolus methods for measuring effective renal plasma flow.

This open-label, three-way crossover study examined the feasibility of measuring effective renal plasma flow (ERPF) using a single intravenous (IV) bolus method. Eight healthy young adults (four women aged 28 +/- 5 years [mean +/- SD] and four men aged 30 +/- 7 years) received on separate days an IV bolus of p-aminohippurate (PAH) 10 mg/kg, an IV bolus of phenolsulfonphthalein (PSP) 1 mg/kg, and the standard constant-rate IV infusion of PAH. The renal clearance (CLR) and plasma clearance (CLP) of PAH after constant infusion were 623.7 +/- 62.9 and 869.0 +/- 58.8 mL/min/1.73 m2, respectively. After PAH bolus injection, CLR and CLP were 538.9 +/- 110.8 and 677.6 +/- 122.4 mL/min/1.73 m2, respectively. After PSP bolus injection, CLR and CLP were 252.8 +/- 57.9 and 350.0 +/- 41.3 mL/min/1.73 m2, respectively. The ERPF measured by PSP bolus injection was significantly lower (P < 0.05) than by PAH infusion. The CLP of PAH after IV bolus injection was significantly lower than after IV infusion when men and women were analyzed together (P < 0.05). However, there appeared to be a greater magnitude of difference between the CLR after IV bolus and infusion of PAH for women than for men. In summary, PSP administered as an IV bolus injection does not appear to be a reliable marker of ERPF. The difference in ERPF determined by the PAH infusion and bolus methods may require further evaluation.

Adult↗
PubMed1994

A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient.

The incidence of vancomycin-associated nephrotoxicity was determined in a younger (age < 60 y) versus elderly (age > or = 60 y) hospitalized adult population to identify associated drug- and nondrug-related risk factors. Nephrotoxicity was defined as an acute increase in serum creatinine of > or = 44.2 mumol/L if baseline serum creatinine was < or = 221 mumol/L or an increase in serum creatinine of > or = 88.4 mumol/L if baseline serum creatinine > 221 mumol/L. A total of 289 patients, 141 younger (mean age, +/- S.D. 37.9 +/- 12.4 y) and 148 elderly (73.6 +/- 8.5 years), was retrospectively reviewed. Nephrotoxicity occurred in 7.8% younger vs 18.9% elderly patients (P = 0.003). Using multivariate logistic regression models for the pooled patient population, concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (relative risk (R.R.) = 5.06); for the younger population, only concurrent amphotericin B use was significantly associated with vancomycin-associated nephrotoxicity (R.R. = 6.65); and for the elderly population, only concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (R.R. = 9.70). These data suggest that elderly patients are at significantly greater risk of vancomycin-associated nephrotoxicity than are younger patients. However, because age was not a significant risk factor for nephrotoxicity in comparing the pooled vancomycin-associated nephrotoxicity group compared to the non-nephrotoxicity group, the differences observed between age groups probably reflect differences in risk factor prevalence.

Adolescent↗
PubMed1994

Bayesian forecasting of serum vancomycin concentrations with non-steady-state sampling strategies.

The application of three non-steady-state sampling strategies and the fitting of either three or five pharmacokinetic parameter estimates by a two-compartment Bayesian forecasting program was evaluated retrospectively in 27 adult patients with stable renal function. Sampling strategies included a single midpoint concentration, a set of peak and trough concentrations, and three serial vancomycin concentrations. The most precise and least-bias predictions of steady-state peak vancomycin concentrations were observed by using population-based parameter estimates [mean prediction error (ME) = -0.40 and mean absolute error = 5.77]. The addition of non-steady-state feedback concentration(s) did not provide additional information for predictions of future steady-state peak concentrations. The least-bias prediction of steady-state trough vancomycin concentrations was seen when a single midpoint non-steady-state concentration was used (ME = 0.92 and -0.17 for five and three fitted parameter estimates, respectively). The MEs of serial and peak and trough feedback strategies were similar in magnitude to those obtained using population parameters, but in opposite directions (underprediction vs. overprediction, respectively). The fitting of only three parameters produced results similar to those using five parameters. The results from this study confirm our previous evaluation that non-steady-state concentrations provide very minimal information to Bayesian forecasting of future steady-state concentrations.

Adult↗
PubMed1994

Amantadine and rimantadine prophylaxis of influenza A in nursing homes. A tolerability perspective.

Amantadine and rimantadine are recommended for the treatment and prophylaxis of influenza A infections, and constitute an integral component of influenza control measures in the nursing home setting. However, optimal use necessitates a thorough understanding of the toxicity profiles of these agents, as well as strategies to reduce the risk of adverse reactions. Adverse reactions of these compounds predominantly involve the gastrointestinal tract and the central nervous system (CNS), including hyperexcitability, slurred speech, tremors, insomnia, dizziness, mood disturbance, ataxia, psychosis and fatigue. Based on data from comparative trials, rimantadine appears to exhibit a lesser propensity to cause adverse CNS reactions than amantadine, but a similar propensity to cause adverse gastrointestinal reactions. Factors enhancing the risk of adverse reactions to these agents include reduced renal function (especially for amantadine), drug-drug interactions with cationic drugs, which inhibit amantadine renal tubular secretion (e.g. trimethoprim, triamterene, and possibly cimetidine and procainamide), elevated peak and trough plasma concentrations, and a history of seizures. Careful attention to published dosage adjustment guidelines for these compounds, avoidance of interacting drugs and avoiding these agents in patients with a history of seizures may be the best means to reduce the risk of toxicity in elderly patients. Rimantadine may have an advantage over amantadine in the elderly population in light of its lesser propensity to cause adverse reactions, less complex dosage adjustment in the case of renal impairment and probable lack of drug-drug interaction potential with cationic drugs.

Aged↗
PubMed1993

Comparison of vancomycin pharmacokinetics in hospitalized elderly and young patients using a Bayesian forecaster.

Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients. This study was designed to assess vancomycin pharmacokinetics in 148 elderly (> or = 60 years of age) and 140 young (18-59 years of age) hospitalized infected patients. Serum vancomycin concentrations were determined using fluorescence polarization immunoassay. Serum concentration-versus-time data were fitted to a two-compartment Bayesian forecasting program. Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine < or = 1.5 mg/dL); mean +/- standard deviation terminal disposition half-life (t1/2) of 17.8 +/- 11.8 versus 7.5 +/- 6.7 hours, respectively, P < .05; volume of distribution (Vz) of 74.2 +/- 32.3 versus 67.0 +/- 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 +/- 0.41 versus 1.22 +/- 0.50 mL/min/kg, respectively, P < .05. Comparing subjects with normal serum creatinine values (< or = 1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 +/- 5.8 verus 25.2 +/- 7.8 mg/kg/day, P < .05). Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance. Age was consistently an independent and significant predictor of t1/2, Vz, and CL. These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and pharmacokinetic parameters.

Adolescent↗
PubMed1993

Overview of the pharmacology of clarithromycin suspension in children and a comparison with that in adults.

The pharmacokinetics of clarithromycin after oral administration of clarithromycin granules for suspension formulation were investigated in adult volunteers and pediatric patients. A 250-mg single dose study conducted in adults revealed that the extent of absorption of clarithromycin from the suspension formulation was not significantly different from that of the reference tablet formulation, whereas the extent of formation of the active 14-hydroxy (14-OH) metabolite was significantly lower with the suspension formulation. In addition coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. A single/multiple dose study conducted in adults revealed a delay in the time to attain peak plasma clarithromycin and 14-OH metabolite concentrations after suspension administration as compared with data obtained after tablet administration in previous studies. Steady state was achieved by Dose 5 in the multiple dose phase (250 mg every 12 hours for seven doses). In addition the mean plasma concentration-vs.-time data after suspension administration compared favorably with that noted after multiple oral dose administration of 250-mg tablets in adults. A single/multiple dose study conducted in pediatric patients revealed that coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. During the multiple dose phase (7.5 mg/kg every 12 hours for 4 or 5 days), mean plasma concentration-vs.-time data compared favorably with that noted after multiple oral dose administration of 250-mg and 500-mg tablets in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors.

OBJECTIVE: To determine the period prevalence of Clostridium difficile disease and asymptomatic carriage in the residents of long-term care facilities (LTCF) and to characterize the risk factors for colonization or associated disease. DESIGN: Period prevalence survey. SETTING: Two long-term care facilities in St. Paul, MN. PARTICIPANTS: Specimens were collected from 225 LTCF residents. MEASUREMENTS: The dependent variable was the culture result for C. difficile, which was isolated and identified using selective culture media and a commercial anaerobe identification kit. Tissue culture assay was used to detect the ability of each C. difficile isolate to produce toxin. Independent variables (including gender, age, race, current medical diagnoses, severity of underlying disease, case mix, current clinical symptoms, current medications, antibiotic use within 4 weeks prior to specimen procurement, and other pertinent history) were obtained from the current medical record of each participant. RESULTS: Of 225 stool cultures that were obtained, 16 (7.1%) were positive for C. difficile. None of the residents with a positive culture was symptomatic. History of nosocomial infection and the use of antibiotics in general, cephalosporins, trimethoprim/sulfamethoxazole (TMP/SMX), and histamine-2 blockers were significantly associated with positive C. difficile culture (P < or = 0.05) by univariate analyses. Trends towards significance (0.05 < 0.10) were noted for narcotic use, previous hospitalization, LTCF, and non-insulin-dependent diabetes mellitus. Logistic regression analysis revealed significant, independent predictors of positive culture: antibiotic use in general (P = 0.028; relative risk = 3.31), histamine-2 antagonist use (P = 0.038; relative risk = 3.27), cephalosporin use (P = 0.038; relative risk = 4.66), and TMP/SMX use (P = 0.007; relative risk = 8.45). CONCLUSIONS: The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.

Aged↗
PubMed1993

Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique.

Few data exist concerning the effect of obesity on the pharmacokinetic parameters of vancomycin. The purpose of this investigation was to assess the effect of obesity on vancomycin pharmacokinetic parameters in 95 nonobese and 135 obese adult patients (age range, 18 to 92 years) receiving vancomycin. All subjects had normal renal function as defined by a creatinine concentration in serum of < or = 1.5 mg/dl (mean estimated creatinine clearance +/- 1 standard deviation, 76 +/- 34; range, 23 to 215 ml/min). Vancomycin concentrations in serum were determined by the fluorescence polarization immunoassay. All data for vancomycin concentration in serum versus time for each course of therapy were fitted by using a two-compartment Bayesian forecasting program. Subjects were stratified into nine groups on the basis of the percent difference between actual body weight (ABW) and lean body weight (LBW) (> -10%, -10 to 0%, > 0 to 10%, > 10 to 20%, > 20 to 30%, > 30 to 40%, > 40 to 50%, > 50 to 60%, > 60%). Analysis of variance with post hoc Scheffe's testing revealed that statistically significant differences occurred in terminal disposition half-life (t1/2 beta) between the extremes of modestly obese (group 4) and morbidly obese (group 9, P < 0.05) patients. Similar analysis with distribution volume (V) identified significant differences in patients at or near their LBW (groups 2 to 4) and patients who were morbidly obese (groups 8 and 9, P < 0.05). Multiple regression models for the pharmacokinetic parameters V, t1/2beta, and vancomycin total body clearance were developed to assess the joint predictive power of LBW, ABW, and percent over LBW, controlling for the effects of age, initial creatinine concentration in serum, initial creatinine clearance, and gender. In the final model for V, both ABW and percent over LBW were independent and significant predictors. For total body clearance, only ABW was significant and predictive. Percent over LBW was a significant and independent predictor of t1/2beta. LBW is not predictive of these pharmacokinetic parameters and should not be used for initial dosing. On the basis of these data, ABW appears to be superior to LBW for calculating initial dose requirements for vancomycin.

Adolescent↗
PubMed1993

Overview of the tolerability profile of clarithromycin in preclinical and clinical trials.

Results of studies conducted to characterise local, systemic, reproductive, and mutagenic effects indicate that the new macrolide antimicrobial clarithromycin is well tolerated within reasonable multiples of the intended clinical dose. No adverse effects of clarithyromycin on male or female fertility, perinatal, or postnatal reproduction were indicated by data from rabbits, mice, rats and macaques. No evidence of mutagenic potential was revealed from various in vitro and in vivo study methodologies. Evidence of low potential for ototoxicity, oculotoxicity, hepatotoxicity and nephrotoxicity was provided in studies involving rats, dogs and primates. In agreement with studies with other macrolides, venous irritation potential for the intravenous lactobionate salt formulation was substantial in rabbit studies. In addition, the safety profile of this agent has been evaluated on the basis of adverse reactions and abnormal laboratory values seen in phase I, II and III international clinical trials conducted in adults. The most frequently reported adverse reactions occurring in 3768 patients receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%). Adverse reactions were not serious and were usually rapidly reversible. The incidence of adverse reactions did not vary with gender, race or age. Adverse reaction rates were comparable to or less than those of comparator beta-lactams and macrolides. Overall, clarithromycin appears to be a safe and well-tolerated macrolide antimicrobial agent.

Animals↗
PubMed1992

Clarithromycin pharmacokinetics in healthy young and elderly volunteers.

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were assessed in 12 healthy young and 12 healthy elderly volunteers after oral administration of a multiple dose regimen of oral clarithromycin (500 mg every 12 hours for 5 doses). Plasma and urine clarithromycin and 14(R)-hydroxyclarithromycin concentrations were determined using high-performance liquid chromatography. The elderly subjects exhibited significantly elevated clarithromycin peak (Cmax) and trough (Cmin) plasma concentrations and area under the plasma concentration-time curve (AUC) compared with young subjects. In addition, the elderly group exhibited a significantly reduced apparent total body clearance (300 +/- 97 versus 476 +/- 112 mL/min, respectively) and renal clearance (CLR) (84 +/- 31 versus 168 +/- 35 mL/min, respectively). Similar results were noted for the 14(R)-hydroxy metabolite, with significantly elevated Cmax, Cmin, and AUC and reduced CLR in the elderly compared with the young group. Because the differences in parent and metabolite pharmacokinetic parameters were small and the increase in circulating drug concentrations was well tolerated (no increase in incidence or severity of adverse events), adjustments in clarithromycin dosing regimens may not be necessary solely on the basis of age.

Administration, Oral↗
PubMed1992

Clarithromycin, a unique macrolide. A pharmacokinetic, microbiological, and clinical overview.

The in vitro and in vivo spectrum of antibacterial activity of clarithromycin is summarized and related to its human pharmacokinetics. In vitro studies by several investigators have documented clarithromycin's activity against bacterial agents of respiratory tract infections, skin and soft tissue infections, and sexually transmitted diseases. Clinical cure rates of 52%-83% (pneumonia), 79%-96% (bronchitis), 82%-96% (pharyngitis), 58% (sinusitis), and 78% (skin/skin-structure infections) have been reported in patients receiving clarithromycin in comparative trials. Respective bacteriologic eradication rates in clarithromycin recipients have been reported as 57%-89%, 79%-96%, 88%-100%, 89%, and 90%. In vitro and in vivo studies suggest that clarithromycin, when combined with its major human metabolite, 14-hydroxyclarithromycin, is also effective against Haemophilus influenzae. A New Drug Application claiming efficacy in the treatment of lower respiratory tract infection, sinusitis, pharyngitis, and skin and skin-structure infections caused by susceptible pathogens has been filed with the Food and Drug Administration (FDA). This review summarizes relevant pharmacokinetic, microbiological, and clinical data for clarithromycin.

Clarithromycin↗
PubMed1992

Comparative safety and efficacy of clarithromycin and ampicillin in the treatment of out-patients with acute bacterial exacerbation of chronic bronchitis.

In an open, randomized trial, adult non-hospitalized patients with acute bacterial exacerbation of chronic bronchitis were treated with 500 mg clarithromycin twice daily (n = 53) or 500 mg ampicillin four times daily (n = 50). Causative pathogens included S. pneumoniae, M. catarrhalis, H. influenzae, H. parainfluenzae and S. aureus. For clinically evaluable patients, successful outcome (cure or improvement) was noted for 53/53 (100%) clarithromycin-treated patients and 46/47 (98%) ampicillin-treated patients. Clinically significant improvement in signs and symptoms was comparable between treatment groups. There was 100% bacteriological eradication in both treatment groups. Eight patients (15%) in the clarithromycin group and 10 patients (20%) in the ampicillin group reported adverse events, the majority of which were mild or moderate in severity; six events in each treatment group were digestive-system disorders. The new macrolide, clarithromycin, appears to be effective and well-tolerated in the treatment of acute exacerbation of chronic bronchitis.

Acute Disease↗
PubMed1992

Safety and pharmacokinetics of multiple doses of intravenous ofloxacin in healthy volunteers.

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval.

Adolescent↗
PubMed1992

The role of the fluoroquinolones.

Over the past decade, the quinolone antimicrobial class has enjoyed a renaissance with the emergence of the fluoroquinolone subclass. Norfloxacin, ciprofloxacin, ofloxacin, enoxacin, and lomefloxacin have the advantages of broad antimicrobial activity profiles including gram-positive and -negative aerobes, favorable pharmacokinetic profiles including substantial oral bioavailability and extensive tissue distribution, and in general, favorable safety profiles. As clinical experience accumulates, our understanding of their optimum roles will become more refined. In six instances, these agents may be preferred over currently available agents: complicated urinary tract infections, empiric therapy of suspected bacterial gastroenteritis, eradication of the Salmonella carrier state, respiratory exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis, invasive external otitis, and chronic gram-negative bacillary osteomyelitis. The efficacy and convenience of these agents for the treatment of a broad range of infections have already resulted in their extensive use. Such use carries the risk of selection pressure for the development of resistance and the adverse consequences of increased cost over less expensive, equally effective alternatives. The use of the fluoroquinolones should focus on infections where there is demonstrated benefit of these agents over conventional agents or infections for which there are few or no alternatives.

Anti-Infective Agents↗
PubMed1992

Amantadine-resistant influenza A in a nursing facility.

Rapid index case treatment and amantadine prophylaxis were implemented in two nursing homes exposed to influenza A. Facility A had no isolation of cases, and 18 of 22 cases occurred after amantadine hydrochloride therapy was initiated. Three patients exhibited amantadine-resistant virus. Facility B had day 1 isolation of the index case. A facility-wide outbreak did not occur. The experience of these facilities suggests that concurrent amantadine treatment and prophylaxis without adequate case isolation may promote further influenza A infection in a nursing facility.

Aged↗
PubMed1991

The influence of age on the pharmacokinetics of temafloxacin.

The pharmacokinetics of temafloxacin were assessed in 12 healthy young and 12 healthy elderly volunteers after oral administration of a single 600 mg dose. Groups were balanced with respect to gender distribution. Plasma and urine temafloxacin concentrations were determined using high-performance liquid chromatography. Compared with the young group, mean peak plasma concentration in the elderly was 45% higher, the area under the plasma concentration versus time curve was 70% higher, the terminal elimination half-life was 18% higher, and the apparent beta-phase volume of distribution was 30% lower in the elderly group. Gender differences were small and largely disappeared when data were normalized to body surface area. As the difference in elimination half-life was small, alteration of the usual twice-daily dosage regimen is not necessary in the elderly. However, elderly patients with decreased renal function (creatinine clearance less than 40 mL/min) will need dosage reduction, similar to that recommended for younger patients.

Absorption↗