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K A Rodvold

Publications and source records attributed to K A Rodvold.

At least 55 records · Page 3Linked to original sources
PubMed1993

Methods of minimising the cost of aminoglycoside therapy to hospitals.

Aminoglycoside agents are used for a wide variety of systemic infections and can profoundly affect hospital expenditures depending upon the amounts used, acquisition costs, and costs incurred during therapy. Significant cost advantages can be gained through selection and proper use of the appropriate aminoglycoside. Institutions can improve the selections by using inservice training and other educational methods, drug-use audits, and therapeutic substitution. Institutions may also restrict or delete certain aminoglycosides from the drug formularies to help minimise costs. Therapeutic drug monitoring can reduce the incidence of aminoglycoside adverse effects. However, some methods of monitoring, such as certain clinical pharmacokinetic services, can be time consuming and require additional manpower. These measures can be shown to be cost effective if they can decrease the length of therapy, minimise toxicity, decrease the length of hospitalisation, or affect mortality. Experimental data and preliminary clinical evidence suggest that once-daily regimens of aminoglycoside agents have some possible advantages over the standard regimens. If this regimen can be widely used, cost savings secondary to decreased use of aminoglycosides can be realised in the future. Potent, broad spectrum beta-lactam monotherapy has threatened to replace conventional combination therapies that include aminoglycosides in some infectious processes and a few studies have found certain single-drug therapies to be cost effective.

Aminoglycosides↗
PubMed1992

Pharmacokinetics of lorazepam in critically ill neonates with seizures.

Pharmacokinetic data were evaluated in 10 term neonates with seizures after intravenous administration of lorazepam, 0.05 mg/kg or 0.1 mg/kg. All seizure activity ceased, with no adverse effects. Pharmacokinetic data revealed a decreased volume of distribution and clearance, and a prolonged half-life in comparison with data from older children and adults. These findings are consistent with physiologic differences in the neonate.

Critical Illness↗
PubMed1992

Phenobarbital pharmacokinetics in obesity. A case report.

A morbidly obese woman [190 kg total bodyweight (TBW)] was admitted to hospital with a rapidly progressing wound infection. Over the next 2 weeks the patient developed congestive heart failure, acute renal failure, septic shock and multiple seizure episodes. Intravenous phenobarbital was added to phenytoin therapy to achieve seizure control. A total loading dose of phenobarbital 3700 mg (19.5 mg/kg TBW) was administered in 3 divided doses. The initial dose of 1100 mg resulted in a serum phenobarbital concentration of 6.3 mg/L 5h postinfusion, a second 1100 mg dose increased the concentration to 13.1 mg/L 1h postinfusion and a final dose of 1500 mg resulted in a 22.5 mg/L concentration at the end of the infusion. A phenobarbital maintenance regimen of 120 mg every 12h was then started. Peak serum concentrations of 19.8 and 17.8 mg/L were measured. All of the available serum phenobarbital concentrations and dosage amounts were fitted with least-squares nonlinear regression analysis to a 1-compartment model. An apparent volume of distribution (Vd) of 154.9L (0.82 L/kg TBW), total body clearance (CL) of 29 ml/min (1.74 L/h) and elimination half-life of 61h were determined. Our case report suggests that the dose of intravenous phenobarbital should be calculated using TBW. Additional studies are needed to precisely define the appropriate dosage weight, serum concentrations and clinical efficacy associated with intravenous phenobarbital in morbidly obese patients.

Adult↗
PubMed1992

Clarithromycin and azithromycin: new macrolide antibiotics.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.

Azithromycin↗
PubMed1991

High-dose carmustine and autologous bone marrow reinfusion in the treatment of refractory or relapsed small cell lung carcinoma.

Fourteen patients with small cell carcinoma of the lung in relapse or with disease refractory to chemotherapy were treated with carmustine (BCNU) at doses of 600 to 1000 mg/m2 intravenously followed by autologous bone marrow transplantation. All patients previously were treated with cyclophosphamide, doxorubicin, vincristine, and etoposide. Seven of the 14 patients responded to the high-dose BCNU (50% response with 95% confidence limits ranging from 23% to 77%). Three patients had a complete response, and four had a partial response. Regrowth of tumor occurred within 60 days of treatment in the responding patients. Death occurred in six patients before the recovery of the platelet count to 50,000 cells/microliters. Although the response rate was high, the toxicity was excessive. In the dosage range of 600 to 1000 mg/m2 in heavily pretreated patients, BCNU is not recommended, but additional investigation may be warranted in patients with central nervous system metastases who previously were treated with radiation therapy.

Adult↗
PubMed1991

A comparative evaluation of the safety and efficacy of cefotetan and cefoxitin in surgical prophylaxis.

Safety and efficacy were evaluated and compared retrospectively in 77 patients who received cefotetan (CTN) and 51 patients who received cefoxitin (CFX) for surgical prophylaxis. Both groups were similar with respect to age and gender. Surgical procedures were similar between groups (e.g., obstetric/gynecologic, renal transplant, colon, exploratory laparotomy, gastroduodenal, hernia repair). Postoperative infectious complications were more common in the CTN group (11.6 percent [9/77]) than in the CFX (7.8 percent [4/51]) group; however, this difference was not statistically significant. A higher incidence of wound infections was noted in the CTN group (5.2 percent [4/77]) than in the CFX group (2.0 percent [1/51]); this difference was also not significant. Patients receiving immunosuppressive therapy were more likely to develop infectious complications when CTN was used for prophylaxis (p = 0.0001). Clinically significant blood loss was not noted during surgery. Elevations in prothrombin times (greater than 1 sec) occurred in 27.3 percent (3/11) of CTN and 11.1 percent (1/9) of CFX patients (not significant). Except for the small subset of patients receiving concomitant immunosuppressive therapy, CTN appeared to be as safe and effective as CFX when used for surgical prophylaxis. Although not statistically significant, the increased incidence of wound infections in the CTN-treated patients requires further study in a prospective randomized comparison.

Adult↗
PubMed1991

An updated comparison of drug dosing methods. Part I: Phenytoin.

The relationship between a dose of phenytoin and the resultant serum concentration is difficult to predict, and numerous dosing methods have been developed to quantify the dose required to achieve a specific concentration. This review brings up to date the earlier article in the Journal regarding predictive algorithms, various pharmacokinetics-based dosing techniques and Bayesian feedback methods for phenytoin dosing. The latest data support the original conclusions that dosing methods for phenytoin which incorporate an individualised approach or Bayesian principles tend to offer results superior to those from predictive algorithms. Bayesian methods have the additional advantage of using only 1 serum concentration, obtained under either steady-state or non-steady-state conditions. There is still a need for future investigations that include prospective evaluations of predictive performance and cost-effectiveness data.

Aging↗
PubMed1991

An updated comparison of drug dosing methods. Part II: Theophylline.

This article updates the previous review in the Journal regarding theophylline dosing methods. Among the predictive algorithms evaluated, the dose-titration scheme of Weinberger and Hendeles was extensively tested in 1073 asthmatic patients. When the scheme was followed appropriately, 78% of initial serum concentrations and 66% of repeat serum concentrations were within the therapeutic range of 10 to 20 mg/L. Several authors have also demonstrated that the 'condition correction factor' method for estimating theophylline clearance is of limited value. The individualised methods of Chiou, Koup and Vozeh have been evaluated in over 300 patients. In addition, numerous authors have reported the relative predictive performance of Bayesian dosing programs for theophylline. All methods continue to be a rapid and accurate means of individualizing dosing requirements for patients with a diverse range of theophylline disposition characteristics. Overall, the Bayesian predictions have been less biased and slightly more precise than the pharmacokinetics-based dosing methods. The most recent cost-effectiveness data has shown that a pharmacokinetic dosing program resulted in fewer toxic serum concentrations (18.9% vs 37.8%), a shorter mean duration of hospital stay (6.3 vs 8.7 days) and more therapeutic concentrations with subsequent oral therapy (71.1% vs 44.4%) than among control patients receiving dosages prescribed by physicians.

Algorithms↗
PubMed1991

An updated comparison of drug dosing methods. Part III: Aminoglycoside antibiotics.

Aminoglycoside antibiotics continue to be useful for the treatment of Gram-negative infections. Available dosing methods include predictive algorithms and nomograms, pharmacokinetics-based dosing methods, and methods that incorporate Bayesian forecasting. The individualised Sawchuk-Zaske and Bayesian methods have been extensively evaluated since the previous review in the Journal. Both methods continue to be rapid and accurate means of individualising dosage requirements for patients with diverse pharmacokinetic profiles. The predictive performance of the Bayesian method can be further enhanced when population-based parameters reflect the patient population being monitored. There are now several cost-effectiveness studies that demonstrate that pharmacokinetic dosing services for aminoglycosides result in cost savings, better therapeutic concentrations, fewer toxic serum concentrations, and shorter mean durations of hospital stay and aminoglycoside therapy. Further studies are needed for cost-effectiveness and comparison of various dosing methods in paediatric and neonatal patients.

Aminoglycosides↗
PubMed1991

An updated comparison of drug dosing methods. Part IV: Vancomycin.

The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing but do not allow for individualisation of dosage. Given these constraints, several investigators have attempted to apply conventional least-squares regression techniques and, more recently, Bayesian methodologies using either 1- or 2-compartment pharmacokinetic models. Comparative information evaluating algorithmic methods demonstrates that those of Moellering and Lake offer the least biased and most precise predictions of vancomycin dosage. Patient individualisation using conventional least-squares methodology offers some improvement over nomogram-based methods, both in predictive performance and in dosage adjustment once serum concentration data are available. Overall, the latest data indicate that regimens which incorporate Bayesian principles tend to give better results than nomogram-based or conventional least-squares dosing methods for this drug. Despite the advances in methods for dosing vancomycin, several questions remain to be answered. A lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome has prompted debate over the need for serum concentration monitoring and, if it is needed, over which patient population would most benefit. Secondly, little comparative information is currently available as to the dosing of vancomycin in paediatric and neonatal patient populations. Several nomograms for initial dosing have been proposed, but only 2 have been subject to subsequent testing. Finally, information regarding cost-effectiveness and the quality of patient outcome is lacking from the current literature.

Bayes Theorem↗
PubMed1990

Clinical pharmacokinetics of daptomycin.

Daptomycin is a new lipopeptide antibiotic for which preliminary pharmacokinetic data in adults have been limited to normal healthy volunteers and patients with renal insufficiency. We report the clinical pharmacokinetics of the first and fifth doses of iv daptomycin 150 mg (2 mg/kg) q24h in a 29-year-old man being treated for a gram-positive cellulitis and thrombophlebitis. Individual pharmacokinetic parameters yielded similar results during doses one and five. The pharmacokinetic profile observed in our patient did not markedly differ from data obtained from healthy volunteers.

Adult↗
PubMed1990

Bayesian forecasting of serum gentamicin concentrations in intensive care patients.

This study retrospectively evaluated the predictive performance of a 1-compartment Bayesian forecasting program in adult intensive care unit (ICU) patients with stable renal function. A comparison was made of the reliability of 3 sets of population-based parameter estimates and 2 serum concentration monitoring strategies. A larger mean error for prediction of peak gentamicin concentrations was seen with literature-derived parameters than when ICU population-based parameter estimates were used. Bias and precision improved when non-steady-state peak and trough concentrations were used to predict those at steady-state; the addition of steady-state values did not provide additional information for predictions once non-steady-state feedback concentrations were incorporated. The addition of 4 serial gentamicin concentrations obtained at both non-steady-state and steady-state did not noticeably improve the predictive performance. The results demonstrate that initial ICU pharmacokinetic parameter estimates for a 1-compartment Bayesian model provide accurate prediction of steady-state gentamicin concentrations. Prediction bias and precision showed the greatest improvement when non-steady-state gentamicin concentrations were used to determine individualised pharmacokinetic parameters.

Adult↗
PubMed1989

Nizatidine suppression of basal gastric acid output: a comparison of two intravenous dosage regimens.

To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg daily dose of nizatidine randomly administered both as 100 mg every 8 hours and 150 mg every 12 hours. No significant differences were observed in the mean pharmacokinetic parameters between the two dosing regimens. Pharmacodynamic parameters for the 100 mg every 8 hours versus the 150 mg every 12 hours regimen were not significantly different except for percent of time during the 24-hour study period that the pH was maintained greater than 4 (43.6 +/- 20.7 versus 34.7 +/- 18.3, P less than .05). A significant relationship was demonstrated for both regimens (P less than .05) between the percent time pH greater than 4 and area under the plasma curve for the 24 hour study period. The lack of a significant difference in nizatidine pharmacokinetics between the two dosage regimens suggests a pharmacodynamic cause for the greater cumulative pH effect of the every 8 hour regimen.

Adult↗
PubMed1989

Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients.

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.

Adult↗
PubMed1989

Evaluation of a two-compartment Bayesian forecasting program for predicting vancomycin concentrations.

The application of a two-compartment Bayesian forecasting program for vancomycin was tested retrospectively in 45 adult patients with stable renal function. Serial blood samples from 25 of these patients were used to determine population-based parameter estimates. The predictive performance of the Bayesian program was assessed by using both non-steady-state and steady-state vancomycin concentrations as feedback information. Overall, the program tended to underpredict peak and trough steady-state vancomycin serum concentrations. A larger mean prediction error (ME) was seen when non-steady-state feedback serum concentrations were used compared with using population-based parameter estimates (no feedback). In contrast, a marked improvement in ME (peaks: -1.03 versus -2.61; troughs: -1.60 versus -2.07) was seen when steady-state feedback serum concentrations were used compared with no feedback data. Precision improved when either feedback serum concentrations were used to predict steady-state peak and trough vancomycin concentrations. The results from this clinical evaluation demonstrate that the initial pharmacokinetic parameter estimates for a two-compartment Bayesian model provided accurate prediction of steady-state vancomycin concentrations. Prediction bias and precision were improved when steady-state vancomycin concentrations were used to determine individualized pharmacokinetic parameters.

Adult↗
PubMed1989

Lidocaine disposition following intravenous regional anesthesia with different tourniquet deflation technics.

It has been claimed that tourniquet cycling, cyclic deflation and reinflation of the tourniquet at the termination of intravenous regional anesthesia (IVRA), enhances the safety of IVRA by minimizing the peak blood level of local anesthetics. To evaluate the validity of these claims and to determine the optimal cycling technic, peak arterial (Cmax) plasma concentrations of lidocaine were determined as well as the time to reach these peaks (Tmax) utilizing contralateral radial arterial blood samples in three groups of volunteers after 30 minutes of IVRA: In all three groups IVRA was induced with 3 mg/kg of lidocaine and maintained for 30 min. In the first group the tourniquet was then simply deflated once (and not reinflated); in the second group the tourniquet was deflated three times with variable periods of deflation (0, 10 and 30 seconds) separated by 1-minute periods of reinflation; and in the third group the tourniquet was again deflated 3 times but with fixed periods of deflation (10 sec) separated by 1 min periods of reinflation. The results obtained indicate that cycling technics do not appear to significantly reduce Cmax, but they do significantly prolong Tmax. Of the two cycling technics, the 10-second deflation interval technic appeared to be superior, both clinically and pharmacologically, as it was associated with less venous congestion and therefore less discomfort, and it sequentially decreased the arterial plasma concentration of lidocaine with each subsequent deflation-reinflation cycle.

Adult↗