The role of the pharmacist in antimicrobial agent therapy.
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Anti-Bacterial Agents↗
Biomedical subjects
R A Prince
Publications and source records attributed to R A Prince.
Penetration of cefotaxime into respiratory secretions.
The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (less than 0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter). Concentrations of desacetyl cefotaxime in lung secretions (6.9 +/- 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 +/- 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime.
Adult↗
Effects of smoking on nortriptyline plasma concentrations in depressed patients.
The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significantly lower than the nonsmokers' mean value of 158 +/- 35 ng/ml. The mean normalized free plasma concentrations for the smokers of 11.4 +/- 3.5 ng/ml was not different from the nonsmokers' mean concentrations of 11.5 +/- 2.6 ng/ml. The smokers had a slightly higher percentage free drug values of 10.2 +/- 4.0% (p = 0.08) as contrasted to 7.4 +/- 1.5% free nortriptyline for the nonsmokers. The nortriptyline half-life figures for both the free and total drug concentrations did not differ. Multiple linear regression analysis utilizing age, smoking status, sex, liver function, and the presence or absence of enzyme-inducing or -inhibiting drugs as the potential independent variables and percentage free nortriptyline or total nortriptyline concentration as the dependent variable, found that smoking status explained 21% of the variation in the percentage free nortriptyline in the patients and 26% of the variation in the total nortriptyline concentrations. These preliminary data suggest that smokers ideally should be dosed at the lower end of the nortriptyline therapeutic range, whereas nonsmokers should be dosed at the upper end to maximize the antidepressant effect and minimize adverse effects.
Adolescent↗
The utility of a single-point dosing protocol for predicting steady-state lithium levels.
Two methods for predicting steady-state serum lithium level were compared prospectively in in-patients suffering from affective disorder. A single-point prospective administration model that required a single 24-hour serum lithium level, following a test dose produced statistically similar predictions of the observed steady-state lithium levels as did a model that required 12- and 36-hour levels. However, the latter two-point method produced significantly more accurate predictions from clinical interpretation. Although the two-point approach is preferable, the single-point method is clinically acceptable if its limitations of accuracy are taken into consideration.
Adult↗
Prospective evaluation of two lithium maintenance dose schedules.
A prospective method for recommending lithium carbonate maintenance doses for patients requiring the drug either prophylactically or for acute mania has been previously described. Of 18 patients who required prophylactic lithium levels between 0.40 and 0.89 mEq/liter, the maintenance dose equation achieved the predefined therapeutic range in 15 (83%) cases. Of 20 patients requiring lithium concentrations between 0.90 and 1.30 mEq/liter for the treatment of acute mania, 17 (85%) attained the therapeutic range after receiving the recommended maintenance dose. The authors discuss the factors that limit the usefulness of this prospective dosing protocol.
Adult↗
Comparison of multiple-point methods for estimating phenytoin maintenance dose requirements.
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Humans↗
Side-effect profiles of newer-generation cephalosporins.
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Cephalosporins↗
Prediction of lithium maintenance doses using a single point prediction protocol.
Conflicting reports regarding the utility of a previously described single point prediction dosing method for lithium prompted the present study's reexamination of the relationship between a single point lithium concentration and the lithium maintenance dose. Seventeen informed, adult patients with affective illness were studied. The relationship between their 24-hour lithium concentration after a test dose and the maintenance dose was significant, hence confirming earlier reports. In addition, more confident relationships were noted when steady state range concentrations for lithium prophylaxis (0.41 to 0.89 mEq/liter) and for treatment of acute mania (0.9 to 1.27 mEq/liter) were analyzed separately. Maintenance dose predictive equations were generated for these lithium steady state ranges from a 24-hour single point level after a 1200-mg test dose. The clinical usefulness of the new relationships observed for maintenance dose prediction must await prospective testing.
Adult↗
Comparative trial of benzoyl peroxide versus benzoyl peroxide with urea in inflammatory acne.
Improvement in vehicle design may improve the delivery of drugs to the target site. A clinical trial was performed to evaluate an improved vehicle for topical benzoyl peroxide. Thirty-nine subjects participated in a split-face, double-blind trial of topical benzoyl peroxide 5 percent versus benzoyl peroxide 5 percent in 8 percent urea. All subjects had grade II or III acne as described by Pillsbury. Study solutions were randomly assigned to a selected side of the subject's face and applied twice a day to the appropriate side of the face for eight weeks. Total and inflammatory lesion counts were performed by the same investigator during the eight weeks of study at biweekly intervals. No overall differences in the response to the study preparations were observed when assessed objectively and subjectively.
Acne Vulgaris↗
Effect of erythromycin on theophylline kinetics.
The effect of erythromycin base on theophylline kinetics was studied in eight informed, nonsmoking, adult males who received a 15-min infusion of theophylline (aminophylline) 5 mg/kg, prior to (control) and after (experimental) a 7-day course of 1 gm daily erythromycin base (E-Mycin). Each subject acted as his own control. Multiple serum samples were collected for 24 hr after each dose and were analyzed for theophylline by high-pressure liquid chromatography. The mean +/- SD pharmacokinetic parameters for each phase of study were as follows: apparent volume of distribution (L/kg) 0.45 +/- 0.05 (control), 0.41 +/- 0.05 (experimental); clearance (ml . min/kg) 0.83 +/- 0.17 (control), 0.60 +/- 0.11 (experimental); elimination half-life (hr) 6.65 +/- 1.88 (control), 8.10 +/- 1.58 (experimental). Erythromycin significantly affected the elimination half-life and clearance of theophylline (p less than 0.05). The apparent volume of distribution was unaffected (p greater than 0.05). Therefore patients being administered theophylline appear to be at added risk for the development of toxicity when erythromycin is added to the therapeutic regimen.
Adult↗
Antimicrobial penetration into cerebrospinal fluid.
The complex physiology of the blood-brain barrier and the characteristics of an antimicrobial which govern its distribution into the brain are poorly understood. Likewise, available data regarding CSF antimicrobial concentrations after extra-CNS administration, as tabulated in this review, are inadequate. Because of the potentially dire consequences that result from inappropriately treated CNS infections, large cooperative studies using standardized methodology are needed. Suggestions for such methods are outlined.
Adolescent↗
Clinical trial of topical erythromycin in inflammatory acne.
Sixty-nine informed subjects participated in a split-face, double-blind trial of topical erythromycin base 2% in Vehicle/N versus Vehicle/N alone. All subjects had grades II or III acne as described by Pillsbury. Study solutions were assigned to a randomly selected side of the subject's face. Solutions were applied twice daily. Inflammatory lesion counts were performed by the same investigator during the eight weeks of study at biweekly intervals. The difference in inflammatory lesion counts from beginning to end of study for each side of the face was compared utilizing Student's paired t-test. There was not a statistically significant difference in mean inflammatory lesions at the end of eight weeks (D = 1.46, t = 1.36, df 68). There was, however, a significant difference at two and six weeks (D = 2.59, t = 3.72, df 68; D = 1.41, t = 2.03, df 68). Observed differences in lesion counts were not considered to be clinically significant.
Acne Vulgaris↗
Comparative trial of two sulfisoxazole regimens in acute urinary tract infection.
Many clinicians are utilizing a 2-g loading dose of sulfisoxazole in the treatment of uncomplicated urinary tract infection. Although some of these clinicians understand the theoretical reasons for not utilizing such a treatment plan, they may be reluctant to depart from the official recommendations for sulfisoxazole because of the lack of supporting clinical data. The findings of this study provide support for the theoretical considerations outlined previously. Also, considering the potential disadvantages of the loading dose employment, for example, source of patient misunderstanding and complicated patient instructions data supporting the omission of a sulfisoxazole loading dose should be most welcome. In conclusion, the study results suggest that the inclusion of a 2-g loading dose of sulfisoxazole in the treatment of this sample of acute, uncomplicated urinary tract infections did not offer any therapeutic benefit.
Acute Disease↗
Effect of bariatric surgery on erythromycin absorption.
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Erythromycin↗
Factors associated with creatinine clearance changes following gentamicin therapy.
The relationship between creatinine clearance changes during gentamicin therapy and several patient and therapeutic variables was studied in a prospective, multicenter trial. Adult patients in three hospitals who were receiving gentamicin in doses based on lean body weight and creatinine clearance were studied. Pre- and post-therapy serum creatinine measurements were obtained for 62 patients (Group 1); only 45 of the patients had both pre- and post-therapy creatinine clearance measurements (Group 2). Other data collected for correlation with creatinine clearance changes were: body temperature, age, sex, blood pressure, albumin level, previous and concomitant therapy with nephrotoxic drugs, hematocrit, peak and trough gentamicin levels, and duration of therapy. In Group 2 patients, only peak gentamicin level, concomitant therapy, sex, and previous furosemide therapy correlated significantly (p less than or equal to 0.05) with change in creatinine clearance during gentamicin therapy. The first two variables decreased creatinine clearance, the last variable increased creatinine clearance, and women tended to have more of a decrease in clearance than did men. Sex, peak gentamicin level, prior furosemide therapy and concomitant cephalothin therapy explain about 50% of the renal function changes during gentamicin therapy, and should be considered in monitoring gentamicin therapy.
Analysis of Variance↗
Use of simulation to develop multiple-dose regimens for drugs exhibiting nonlinear elimination kinetics.
A mathematical model and resulting computer program for simulating blood-level versus time profiles of drugs exhibiting saturable elimination processes are described and evaluated. The iterative digital-analog simulator (IDAS) program consists of two sections--a simulation (SIM) module and an iteration control (IC) module. The SIM module predicts minimum and maximum serum drug levels based on a dose and a dosing interval. The IC module takes the minimum and maximum serum levels from the SIM module and produces a new dose (for a new maximum serum level) and a new dosing interval (for a new minimum serum level). The new dosing information is fed back into the SIM module and the iteration process is repeated until the predicted minimum and maximum levels converge on desired levels set by the user of the program. The model and program were tested by comparing simulation results with actual patient data for phenytoin (seven patients) and theophylline (three patients). The ability of the program to converge on correct doses and dosing intervals was evaluated under a variety of given conditions. The mean difference between actual and simulated profiles was 0.286 mg/liter and 1.5 mg/liter for phenytoin and theophylline, respectively. IDAS produced dose and dosing interval estimates within desired precision given a variety of initial input data. The results encourage prospective clinical investigation of the reliability and validity of the method.
Computers, Hybrid↗