Category Archives: Pharmacokinetics

Hello 1.2!

App Store, Pharmacokinetics, RxCalc

It’s been a few months in the making but RxCalc 1.2 is now available in the App Store.

What’s new? Glad you asked. There are two new features to talk about.

  1. Support for dosing adjustment using single level vancomycin kinetics.
    • The calculations are performed using both patient specific information supplied by the user as well as patient population parameters.
  2. Literature supported High Dose Extended Interval (HDEI) (aka “once daily” or “pulse”) aminoglycoside dosing.
    • Calculations for gentamicin and tobramycin are based on 7mg/kg adjusted body weight.
    • Calculations for amikacin are based on 15mg/kg adjusted body weight.

This release was also unique because we finally opened the door to a Beta Tester. Our heartfelt thanks goes out to Robert B. Martin, Pharm.D. Robert provided a critical eye for Jerry’s Pharmacokinetic Calculations and his years of clinical experience were priceless. He’s given us a lot of great feedback we’ll be sure to include in future releases. That’s right, we like to hear from our users!

We hope you enjoy using 1.2 as much as we enjoyed developing it.

Introducing RxCalc 1.1

Pharmacokinetics, Pharmacy, RxCalc

RxCalc 1.1When we released RxCalc 1.0 we felt the need to focus most of our effort on making sure our math was correct. We felt if the standard user interface was good enough for Apple, it was good enough for us. Since that time we’ve collected a bit of feedback, some great, some not so great, and a couple of really horrible comments that made us cringe. Fear not! We picked ourselves up off the ground, regrouped, and went to work on RxCalc 1.1. We hope you enjoy using it as much as we enjoyed developing it.

What’s New in 1.1?

Options

  • User configurable Units of Measure
    1. Height
    2. Weight
    3. Serum Creatnine
  • Configurable Volume of Distribution
    1. Aminoglycoside
    2. Vancomycin
  • Less rigid scrolling
  • Less rigid data entry

The big addition is the user configurable Units of Measure and adjustable Volume of Distribution. These should help folks outside the United States and gives flexibility to those that would like to modify the default Volume of Distribution values. We’re also really happy with the new navigation experience. Version 1.0 was a bit rigid, we’ve changed that. You can now freely move between entry fields and scroll top to bottom with complete freedom, while the keyboard is showing.

Oh, yeah, it also has a great new icon! Courtesy of our good friend, Mr. Layne Lev.

Cockcroft-Gault equation remains an effective way to estimate GFR

aminoglycosides, Pharmacokinetics, ,

From The Annals of Pharmacotherapy Vol. 44, No. 6, pp. 1030-1037:

Evaluation of Aminoglycoside Clearance Using the Modification of Diet in Renal Disease Equation Versus the Cockcroft-Gault Equation as a Marker of Glomerular Filtration Rate

BACKGROUND: Accurate estimation of kidney function is essential for safe administration of renally cleared drugs. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault (CG) equation as an estimation of glomerular filtration rate. Few data exist regarding the utility of the Modification of Diet in Renal Disease (MDRD) equation in drug dosing.

OBJECTIVE: To evaluate glomerular filtration rate based on creatinine clearance (CrCl) derived from the MDRD or the CG equation compared with patient-specific CrCl calculated from aminoglycoside peak and trough concentrations.

METHODS: Medical records of patients who received aminoglycoside antibiotics were reviewed over 1 year. Patients who received aminoglycosides via conventional dosing with peak and trough concentrations at steady state were included. Calculations based on standard pharmacokinetic equations were used to estimate CrCl from aminoglycoside serum concentrations. Patient-specific CrCl estimated from aminoglycoside concentrations was compared with estimated CrCl from the CG or MDRD equation.

RESULTS: Fifty-five patients were included in the final analysis. The primary outcome showed concordance between estimated and actual aminoglycoside clearance was 0.53 (95% CI 0.18 to 0.88) for the CG equation and 0.41 (95% CI 0.04 to 0.78) for the MDRD equation. Subgroup analysis also favored CG as a better predictor of CrCl. This signified a stronger correlation between the CG equation and aminoglycoside clearance.

CONCLUSIONS: Compared with the MDRD equation, the CG equation provided better correlation of estimated glomerular filtration rate for aminoglycoside antibiotics. Institutions should continue to use the CG equation as the standard of practice to safely adjust aminoglycoside doses in patients with renal dysfunction.

It appears that the Cockcroft-Gault (CG) equation remains an effective way to estimate GFR for aminoglycoside PK calculations. I’ve been using the CG equation since my pharmacy school days and have no immediate plans to make a change.

Evaluation of once-daily gentamicin dosing in children with febrile neutropenia

aminoglycosides, cancer, gentamicin, neutropenia, once-daily dosing, pediatrics, Pharmacokinetics

Once-Daily Gentamicin Dosing in Children with Febrile Neutropenia Resulting from Antineoplastic Therapy

Miriam Inparajah, B.Sc.Phm. | Cecile Wong, B.Sc.Phm. | Cathryn Sibbald, B.Sc.Phm. | Sabrina Boodhan, B.Sc.Phm. | Eshetu G. Atenafu, M.Sc. | Ahmed Naqvi, M.B.B.S., MCPS, MRCP | L. Lee Dupuis, M.Sc.Phm., FCSHP

Pharmacotherapy. 2010 Jan;30(1):43-51

Abstract

Study Objectives. To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose.

Design. Pharmacokinetic analysis of data froma retrospective medical record review.

Setting. Hematology-oncology unit of a university-affiliated pediatric hospital in Canada.

Patients. One hundred eleven patients aged 1–18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose.

Measurements and Main Results. Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (Cmax) values below the target range (20–25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a Cmax of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioningmethod was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a Cmax within or above target in 73% of patients: 1 year to 6 years, 10.5mg/kg/dose; girls ≥ 6 years, 9.5mg/kg/dose; and boys ≥ 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125%ormore of ideal body weight.

Conclusion. The initial gentamicin dosing guidelines were not effective in achieving Cmax. The new proposed dosing guidelines are predicted to achieve a Cmax within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.

Summary of Consensus Recommendations for Vancomycin Monitoring in Adults

Pharmacokinetics, Vancomycin

A recent article in November 2009 issue Pharmacotherapy summarizes the recommendations from the American Society of Health-System Pharmacists, the Infections Diseases Society of America, and the Society of Infectious Diseases Pharmacists on the monitoring of vancomycin in adults.

“The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists published a consensus statement on therapeutic monitoring of serum vancomycin levels in adults. These organizations established an expert panel to review the scientific data and controversies associated with vancomycin monitoring and to make recommendations based on the available evidence. As the members of this panel, we summarize the conclusions and highlight the recommendations from the consensus statement. We determined that the area under the concentration-time curve (AUC):minimum inhibitory concentration (MIC) ratio is the most useful pharmacodynamic parameter to predict vancomycin effectiveness and suggested a target ratio of 400 or greater to eradicate S. aureus. In addition, trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels. Increasing trough concentrations to 15–20 mg/L to attain the target AUC:MIC ratio may be desirable but is currently not supported by clinical trials. Alternative therapies should be considered in patients with S. aureus infections that demonstrate a vancomycin MIC of 2 mg/L or greater because the target AUC:MIC ratio ( 400) is unlikely to be achieved in this setting. Increasing the dosage to result in higher trough concentrations may increase the potential for toxicity; however additional clinical experience is required to determine the extent.”

While the article contains nothing new in terms of vancomycin monitoring and kinetics, the recommendation to consider alternate therapy for S. aureus infections with an MIC >/= 2 mg/L is important to note.

Can antibiotic choice be based on MIC alone?

MIC, Pharmacodynamics, Pharmacokinetics

This questions was recently addressed by Michael J. Postelnick, Senior Infectious Diseas Pharmacist of Northwestern Memorial Hospital in Chicago, Illinois in an Ask-the-Experts post on the Medscape website. Postelnick gives a good explanation of how various pharmacokinetic and pharmacodynamic principles are related to antibiotic choice for infectious pathogens. According to Postelnick “research into antimicrobial pharmacokinetics and pharmacodynamics has established surrogate relationships between the 2 that correlate with outcomes such [as] bacterial eradication or clinical cure. These relationships include the ratio of Cmax to the MIC, time above the MIC (defined as the amount of time during the dosing interval that the antimicrobial concentration in the blood or at the site of infection remains above the MIC of the organism), and the ratio of the AUC to the MIC. For concentration-dependent antimicrobial agents such as fluoroquinolones and aminoglycosides, Cmax/MIC or AUC/MIC most closely correlates with clinical and microbiological outcomes. For time-dependent antimicrobial agents such as beta-lactams, the percentage of time during the dosing interval that the drug concentration remains above the MIC of the organism is the measure that most closely predicts outcomes.” In other words, selection of an antibiotic requires more than the MIC. Knowledge of the organism in addition to pharmacokinetic and pharmacodynamic principles of the drug is necessary to make an informed choice.