Biomedical subjects

R D Pryka

Publications and source records attributed to R D Pryka.

9 recordsLinked to original sources

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

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

Individualizing vancomycin dosage regimens: one- versus two-compartment Bayesian models.

The absolute and relative predictive performances of one- and two-compartment Bayesian forecasting models were evaluated and compared. Initial population parameters were derived from 25 adult patients with stable renal function and who were being treated for presumed or documented gram-positive infections. The performance of each model was compared using these population parameters with and without steady-state or non-steady-state feedback concentrations to predict future peak and trough concentrations in an additional 20 patients. Both models tended to underpredict vancomycin peak and trough concentrations obtained at steady state. The use of a two-compartment model resulted in statistically less bias and more precise predictions of vancomycin peak concentrations when either population parameters or non-steady-state concentrations were used for future predictions. No difference in model performance was observed when steady-state concentrations were used to predict future steady-state concentrations. The results of this evaluation demonstrate that the two-compartment Bayesian model is less biased and more precise in determining future vancomycin serum concentrations given only population parameters or non-steady-state feedback information. No difference in model performance could be discerned when steady-state concentrations were used as feedback information.

Adolescent↗

PubMed1988

Teicoplanin: an investigational glycopeptide antibiotic.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, adverse effects, and clinical uses of teicoplanin are reviewed. Teicoplanin, a novel glycopeptide that is similar to vancomycin, was isolated in the mid-1970s. A fermentation product of Actinoplanes teicomyceticus, teicoplanin is a structurally complex compound made up of six fatty-acid components attached to a common aglycone. Teicoplanin's mechanism of action, like that of vancomycin, is inhibition of cell-wall biosynthesis. In vitro activity is comparable to that of vancomycin and includes staphylococci, streptococci, corynebacterium, listeria, and anaerobic cocci. Resistance to teicoplanin has been reported with coagulase-negative staphylococci. Teicoplanin is 50 to 100 times more lipophilic than vancomycin. Teicoplanin is poorly absorbed after oral administration but is 90% bioavailable when administered intramuscularly. The drug distributes widely into body tissue and is eliminated primarily renally. Optimal dosing regimens and therapeutic serum drug concentrations have not been well established. Reported adverse effects have included irreversible ototoxicity, allergic reactions with maculopapular rash and eosinophilia, pain at intramuscular injection site, and elevation of aminotransferases. Initial clinical trials have yielded conflicting results in gram-positive bacteremia, endocarditis, osteomyelitis, and soft-tissue infections. Teicoplanin has shown promise in surgical and dental prophylaxis. Comparative trials with vancomycin and other antimicrobial agents must be completed before teicoplanin's role as a therapeutic agent in the treatment of systemic gram-positive infections is defined.

Animals↗