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K A Rodvold

Publications and source records attributed to K A Rodvold.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bayesian forecasting of serum vancomycin concentrations in neonates and infants.

A dynamic pharmacokinetic model for i.v. vancomycin administration was developed and tested in 47 neonates and infants. Twenty-nine patients (Group 1), having two or more concentrations, were used to estimate population parameters by nonlinear least-squares analysis. Multiple stepwise linear regression techniques showed that estimated creatinine clearance, Clcr, and postnatal age were significant demographic factors related to vancomycin clearance (CL). No strong associations were found for the apparent volume of distribution. A one-compartment model was constructed using the associations of CLcr and postnatal age with vancomycin CL. Eighteen patients (Group 2), receiving 35 courses of vancomycin therapy, with both initial and subsequent sets of peak and trough concentrations, were used to test the predictive performance of the model with and without the use of Bayesian forecasting. Using only population-based parameters, the respective mean error (ME) (bias) and mean absolute error (MAE) (precision) for predicting subsequent peak concentrations were -1.20 and 3.89 mg/L and for trough concentrations, 0.83 and 2.23 mg/L, respectively. For the Bayesian method, these values were, respectively, 0.45 and 4.13 mg/L for peak concentrations and 1.55 and 2.40 mg/L for trough concentrations. When predicted concentrations occurred within 30 days of feedback concentrations, the Bayesian method tended to be slightly less biased and more precise than the population-based parameters. The opposite was true > 30 days of the initial set of feedback concentrations. The use of population-specific pharmacokinetic parameters and Bayesian forecasting should allow accurate dosage regimen design as well as minimize the need for monitoring serum vancomycin concentrations in neonates and young infants.

Bayes Theorem↗
PubMed1995

Piperacillin/tazobactam: a new beta-lactam/beta-lactamase inhibitor combination.

OBJECTIVE: To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactan/beta-lactamase inhibitor combination. DATA SOURCES: Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer. STUDY SELECTION: In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed. DATA SYNTHESIS: The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin. CONCLUSIONS: The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase-producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

Bacterial Infections↗
PubMed1994

The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer.

BACKGROUND: The authors compared the pharmacokinetics of doxorubicin when administered with and without concomitant high dose cyclosporine for multidrug resistant (MDR) tumor modulation in small cell lung cancer. METHODS: Eight patients with small cell lung cancer served as their own controls and were studied first during an initial course of doxorubicin without cyclosporine, and then subsequently during a cyclosporine-modulated doxorubicin course. All patients received cyclophosphamide and vincristine in each course. Doxorubicin was administered as a 1-hour infusion after a 2-hour cyclosporine loading infusion, and cyclosporine was infused continuously for the next 48 hours. Serum concentrations of doxorubicin, doxorubicinol, and cyclosporine all were assayed by high-pressure liquid chromatography. Pharmacokinetic analysis of doxorubicin included area under the curve (AUC), clearance, apparent volume of distribution at steady state (Vss), and elimination half-life (T1/2). The percent of change and surviving fraction of leukocyte count and platelets were determined as pharmacodynamic indices. RESULTS: Cyclosporine modulation increased the AUC0-36 of doxorubicin by 48% (P = 0.042) and the AUC0-36 of doxorubicinol by 443% (P = 0.0001), whereas the doxorubicin clearance declined by 37% (P = 0.0495). No difference was found in the Vss or T1/2 for doxorubicin when cyclosporine was added to the regimen. The ratio of the doxorubicinol AUC0-36 to the doxorubicin AUC0-36 increased significantly with cyclosporine modulation (8.88 vs. 2.19; P = 0.001). Drug-related toxicity was also greater with the cyclosporine-modulated course of doxorubicin. A 91% reduction in the leukocyte count followed the modified course, compared with an 84% reduction following the initial course (P = 0.0074). A more prolonged and greater degree of myelosuppression was observed and a significant relationship was found between the systemic exposure to doxorubicin (defined by AUC) and the surviving fraction of the leukocyte count (r = -0.69; P = 0.006). Similarly, the reduction in the platelet count was significantly greater after the cyclosporine-modulated course (72.8%) than after the initial course (36.4%) (P = 0.0016). A significant correlation was found between the AUC of doxorubicinol and the surviving fraction of platelets (r = -0.71; P = 0.004). In addition, patients showed decreased performance status associated with significant weight loss and severe myalgias. CONCLUSIONS: The addition of high dose cyclosporine for MDR modulation resulted in the significant alteration of doxorubicin disposition and remarkable toxicity in all patients. The mechanisms responsible for the decreased doxorubicin clearance may include cyclosporine's ability both to interfere with P-glycoprotein in normal tissues and to selectively inhibit the cytochrome P-450 enzyme system. Further study of this potentially significant drug-drug interaction is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
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

Penetration of clarithromycin into lung tissues from patients undergoing lung resection.

The concentrations of clarithromycin and its active principal metabolite, 14-(R)-hydroxy-clarithromycin, were determined in lung tissue obtained during lung resection and compared with concomitant concentrations in plasma. Concentrations of the parent and metabolite were determined by high-performance liquid chromatography. The 15 patients studied were given 500 mg orally every 12 h for a minimum of five doses to achieve steady-state concentrations. The mean concentrations of clarithromycin and 14-(R)-hydroxy-clarithromycin in plasma just prior to the final dose were 1.38 and 0.67 micrograms/ml, respectively, and those 4 h after the final dose (at the time of lung resection) were 1.89 and 0.80 microgram/mL, respectively. The concentrations of the parent and metabolite in lung tissue at the time of lung resection averaged 54.3 and 5.12 micrograms/g, respectively, with a mean calculated ratio of concentrations of the parent to metabolite being 11.3 in lung tissue and 2.4 in plasma. Clarithromycin and its active metabolite are extensively distributed into human lung tissue.

Adolescent↗
PubMed1994

Steady-state pharmacokinetics of cefoperazone and sulbactam in patients with acute appendicitis.

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean +/- SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2 beta), clearance (Cl), and area under the curve (AUC0-t) were 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/- 122.0 mg.h/L, respectively. Sulbactam Vssd, t1/2 beta, Cl, and AUC0-t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64.8 +/- 24.5 mg.h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2 beta in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

Acute Disease↗
PubMed1994

Cost considerations in therapeutic drug monitoring of aminoglycosides.

Aminoglycoside antibiotics are very important in the treatment of Gram-negative infections and as synergistic agents for the treatment of staphylococcal and streptococcal (group B streptococci and enterococci) infections. However, these agents have a narrow therapeutic index. Thus, a number of new antibiotics have been introduced in an attempt to reduce the number of patients treated with aminoglycosides. Unfortunately, these new antibiotics tend to be costly, and are often associated with development of resistance and treatment failure. Data suggest that a pharmacokinetic/pharmacodynamic relationship exists for some aspects of efficacy and toxicity of aminoglycosides. Serum drug concentrations and/or tissue accumulation are related to the development of nephrotoxicity, and individualised pharmacokinetic monitoring may decrease rates of nephrotoxicity. Peak serum drug concentrations and the ratio of peak serum drug concentration to minimum inhibitory concentration appear to correlate with clinical efficacy in the treatment of patients with bacteraemia or pneumonia. Therapeutic drug monitoring (TDM) has been used to optimise aminoglycoside therapy and reduce toxicity. Cost-effective approaches to drug selection and TDM are important considerations in the proper use of aminoglycosides.

Aminoglycosides↗
PubMed1994

Prediction of acetaminophen concentrations in overdose patients using a Bayesian pharmacokinetic model.

A pharmacokinetic program using population-based parameter estimates and a Bayesian forecasting model was retrospectively evaluated for predicting acetaminophen serum concentrations in overdose patients. Dynamic disposition factors known to affect acetaminophen disposition (emesis, activated charcoal, N-acetylcysteine, etc.) were included in the program. Twenty six patients who reported an acetaminophen ingestion of at least 70 mg/kg within 24 h of presentation to the hospital and had at least one measured acetaminophen concentration were included. Prediction of initial acetaminophen concentrations using only population-based parameter estimates resulted in a percent mean error (%ME) and percent mean absolute error (%MAE) of 9.3 and 42.2, respectively. Using only the initial concentration as feedback, the Bayesian forecasting model accurately predicted the second acetaminophen concentration (%ME = 4.0, %MAE = 23.6). The Bayesian model also accurately predicted all concentrations within 8 h of the ingestion (%ME = 10.6, %MAE = 24.0). The prediction of concentrations between 2 to 4 h and 4 to 4.5 h after ingestion with only population-based parameter estimates resulted in %ME of 17.0 and 13.2, respectively, and %MAE of 36.5 and 35.1, respectively. Our data suggests that acetaminophen serum concentrations occurring within the first 4.5 h after ingestion can be reliably predicted by the set of population-based parameter estimates evaluated. Once a single acetaminophen concentration is available, the Bayesian forecasting model can accurately predict subsequent concentrations within the first 8 h after an acetaminophen ingestion.

Acetaminophen↗
PubMed1993

The disposition of doxorubicin on repeated dosing.

Twelve cancer patients (aged 49-74 years) receiving doxorubicin (66 +/- 8 mg/m2) as a 1-hour intravenous infusion had serial serum samples (0-48 hours) obtained after the first and second courses of therapy. Mean number of days between courses was 24.3, and all patients had normal liver function. Patients received the same concomitant antineoplastic agents and doses in both courses. Doxorubicin and doxorubicinol concentrations were assayed by high-performance liquid chromatography and fitted to a two- or three-compartment infusion model. White blood cell and platelet toxicity were evaluated as (initial--nadir/initial)* 100. Differences in pharmacokinetic parameters were determined by a paired t test. Wide intrapatient and interpatient variability was seen between therapeutic courses. A significant decrease in the apparent volume of distribution of the central compartment (Vc = 16.6 versus 10.4 L/m2; P < .05), and a nonsignificant decrease in clearance (CL = 748 versus 658 mL/min/m2) was observed on the second course of therapy. Doxorubicinol area under the curve and elimination half-life were similar between courses. Extensive chemotherapy-induced changes in white blood cell and platelet counts were observed but were similar in degree for courses 1 and 2. These data suggest that higher initial doxorubicin concentrations on the second course of therapy are secondary to an alteration in distribution volume (Vc). In this subset of patients, however, these changes were not associated with an increase in hematologic toxicity.

Aged↗
PubMed1993

Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer.

The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small lung cell cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p < 0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng.hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.

Aged↗
PubMed1993

New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety.

During the past decade, there has been a resurgence of interest in the development of oral macrolide and fluoroquinolone antimicrobial agents. Azithromycin and clarithromycin are two new oral macrolides whose pharmacokinetics (compared with those of erythromycin) are characterized by improved oral bioavailability, increased tissue penetration and persistence, and longer elimination half-lives. A limited number of interactions with other drugs have been reported for azithromycin and clarithromycin. The most common adverse reactions to the new macrolide agents include nausea, diarrhea, and abdominal pain. Norfloxacin, ciprofloxacin, ofloxacin, temafloxacin, and lomefloxacin are the oral fluoroquinolones that have been marketed in the United States thus far. In comparison to nalidixic acid, the newer fluoroquinolones have improved pharmacokinetic properties, including greater oral absorption, increased peak serum concentrations and areas under the curve, higher tissue concentrations, and longer elimination half-lives. Divalent or trivalent cations can alter the absorption of all fluoroquinolones. Some of the fluoroquinolones (norfloxacin, ciprofloxacin, and ofloxacin) can inhibit the cytochrome P-450 enzyme system and thereby cause increased serum concentrations of drugs like theophylline and caffeine. Adverse reactions to the fluoroquinolones primarily involve the gastrointestinal system, skin, and central nervous system.

Administration, Oral↗
PubMed1993

Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery.

The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB. Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery. Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery. The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively. The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure. The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively. These values were similar to those reported in the literature for children not undergoing CPB surgery. A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure. To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose.

Cardiopulmonary Bypass↗
PubMed1993

Bayesian forecasting of gentamicin pharmacokinetics in pediatric intensive care unit patients.

The predictive performance of a one compartment Bayesian forecasting program was evaluated in pediatric intensive care unit patients with normal renal function. Gentamicin pharmacokinetic parameters were determined in 44 PICU patients (0.8 month to 14 years old) from all available serum concentrations and doses by nonlinear least squares regression. Population pharmacokinetic parameter estimates were established from 27 of the PICU patients. Mean prediction error (ME) and mean absolute error (MAE) for 2 future sets of peak and trough gentamicin serum concentrations with the use of the population parameter estimates with and without feedback were evaluated in the remaining 17 patients. Mean clearance (+/- SD) and volume of distribution for all 44 patients were 0.123 +/- 0.041 liter/hour/kg and 0.424 +/- 0.116 liter/kg, respectively. Bayesian forecasting of the second set of peak and trough concentrations with feedback from the first set of peak and trough concentrations resulted in smaller bias (peak ME, -0.15 mg/liter; trough ME, 0.13 mg/liter) and better accuracy (peak MAE, 0.91 mg/liter; trough MAE, 0.28 mg/liter) compared with the population parameter estimates alone (peak ME, 0.4 mg/liter; trough ME, 0.28 mg/liter; peak MAE, 1.21 mg/liter; trough MAE, 0.57 mg/liter). This study indicates that gentamicin volume of distribution in PICU patients is larger than non-PICU literature values. The Bayesian program, with specific population parameter estimates for PICU patients, provides accurate initial and subsequent predictions of gentamicin serum concentrations.

Adolescent↗
PubMed1993

Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin disposition.

The pharmacokinetic parameters of intravenous ciprofloxacin were examined in five adult male patients on three separate occasions of open heart surgery: the 24 h before cardiopulmonary bypass (CPB) surgery, (PRE), during surgery (SURG), and 48 to 72 h after surgery (POST). Serial blood (n = 16), urine, and SURG tissue samples were collected after intravenous administration of a single 300-mg dose of ciprofloxacin during each study period. All samples were assayed for ciprofloxacin by a specific high-performance liquid chromatographic method. Serum ciprofloxacin concentrations remained constant or continued to decline during the course of CPB surgery. A significant (P < 0.05) decrease in total body clearance was observed during the SURG and POST phases (298 and 306 ml/min/1.73 m2, respectively) compared with that during the PRE phase (364 ml/min/1.73 m2). Renal clearances and elimination half-lives were similar during all three study phases. A nonsignificant decline occurred in the apparent volume of distribution, from mean values of 2.1 and 2.0 liters/kg during the PRE and POST phases, respectively, to 1.7 liters/kg during the SURG phase. The mediastinal fat tissue ciprofloxacin concentrations ranged from 0.45 to 2.89 micrograms/g. Overall, little significant difference was noted in the disposition of intravenous ciprofloxacin during CPB surgery compared with that before and after surgery.

Adipose Tissue↗
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

Prediction of gentamicin concentrations in neonates and infants using a Bayesian pharmacokinetic model.

This study retrospectively characterized population-based pharmacokinetic parameters for gentamicin in neonates and young infants, and evaluated the predictive performance of these parameters in a Bayesian forecasting program. Population parameter estimates were determined from the serum concentration-time data of 19 neonates and infants using a one-compartment open infusion model and nonlinear least-squares regression analysis. Univariate and multiple stepwise linear regression analyses were used to determine significant relationships between demographic characteristics and gentamicin pharmacokinetic parameters. Creatinine clearance and postnatal age were the most significant predictors of weight-standardized gentamicin clearance (model r2 = 0.86). The relationships between patient characteristics and population-based parameters were incorporated into the one-compartment Bayesian forecasting model. A second group of 17 neonates and infants receiving 35 courses of gentamicin therapy were used to evaluate the predictive performance of the population-based parameters and a Bayesian forecasting model. The population parameters provided accurate prediction of steady state gentamicin concentrations throughout multiple courses of therapy within the same patient. Bayesian forecasting further minimized the mean prediction error (bias) once a set of steady state peak and trough serum gentamicin concentrations became available (peak concentrations: -0.062 vs. -0.273 mg/l; trough concentrations: -0.006 vs. -0.161 mg/l). The mean absolute error (accuracy) was similar for the two sets of parameters. The observed accuracy of both the population parameters and Bayesian forecasting suggests that monitoring of serum gentamicin concentrations can be kept to minimum in neonates and infants.

Aging↗