Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center.

AIMS AND OBJECTIVES: Vancomycin is a drug of choice for various gram-positive bacterial (GPB) infections and is largely prescribed to pediatric intensive care unit (PICU) patients. Despite the different pathophysiology of these patients, limited data are available on pharmacokinetics of vancomycin. There are lack of data for critically ill Indian children; hence, study was conducted to assess the steady-state pharmacokinetics in children admitted to PICU. MATERIALS AND METHODS: Twelve subjects (seven males, five females) aged 1-12 years were enrolled. Vancomycin (dose of 20 mg/kg per 8 hours) was infused for over 1 hour and steady-state pharmacokinetics was performed on day 3. Vancomycin concentrations were measured by the validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO). RESULTS: The steady-state mean C ssmax was 40.94 µg/mL (±15.07), and mean AUC0-8 hours was 124.15 µg/mL (±51.27). The mean t 1/2 was 4.82 hours (±2.71), Vd was 12.48 L (±4.43), and Cl was 2.08 mL/minute (±0.89). The mean AUC0-24 among 12 subjects was 372.44 µg/mL (±153.82). Among 35 measured trough concentrations, 23 (65.71%) were below, 11 (31.43%) were within, and 1 (2.86%) was above the recommended range. CONCLUSION: The pharmacokinetic parameters of vancomycin were comparable with previously reported studies. However, recommended trough levels (10-20 µg/mL) were not achievable with current recommended dosing of 60 mg/kg/day. HOW TO CITE THIS ARTICLE: Mali NB, Tullu MS, Wandalkar PP, Deshpande SP, Ingale VC, Deshmukh CT, et al. Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center. IJCCM 2019;23(11):497-502.

Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India.

RATIONALE: Vancomycin remains the standard of care for gram-positive bacterial infections, though there are significant developments in newer antibacterial agents. Efficacy can be improved by linking pharmacokinetic with pharmacodynamic principles, thus leading to optimum antibiotic exposure. There is scarcity of pharmacokinetic data in Indian intensive care unit (ICU) population. MATERIALS AND METHODS: Fifteen subjects with suspected or proven gram-positive bacterial infection of either gender between 18 years and 65 years of age were enrolled. Vancomycin at the dose of 1 g every 12 hours was administered over 1-hour period and pharmacokinetic assessments performed on blood samples collected on days 1 and 3. Vancomycin concentrations were measured on validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO). RESULTS: The mean C max, elimination half-life, AUC0-12hours, volume of distribution, and clearance of single dose were 36.46 µg/mL (±14.87), 3.98 hours (±1.31), 113.51 µg/mL (±49.51), 52.01 L (±31.31), and 8.90 mL/minute (±3.29), respectively, and at steady state were 40.87 µg/mL (±19.29), 6.27 hours (±3.39), 147.94 µg/mL (±72.89), 56.39 L (±42.13), and 6.98 mL/minute (±4.48), respectively. The elimination half-life increased almost two-fold at steady state. The steady state mean AUC0-24 was 295.89 µg/mL (±153.82). Out of 45 trough levels, 32 (71.11%) concentrations were below recommended range. CONCLUSION: Recommended AUC0-24hours and trough concentrations were not achieved in majority of patients with current dosing, suggesting reevaluation of current vancomycin dosing. Individualized treatment based on close monitoring of vancomycin serum concentrations in critically ill patients is imperative. HOW TO CITE THIS ARTICLE: Mali NB, Deshpande SP, Wandalkar PP, Gupta VA, Karnik ND, Gogtay NJ, et al. Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India. IJCCM 2019;23(11):513-517.

A Prospective Antibacterial Utilization Study in Pediatric Intensive Care Unit of a Tertiary Referral Center.

PURPOSE: Antibacterials are commonly prescribed to Pediatric Intensive Care Unit (PICU) patients. However, inappropriate antibacterial prescriptions lead to increases in antibacterial resistance, treatment cost, duration of treatment, and poor clinical outcome. The antibacterial utilization study assesses the prescription patterns and if necessary recommends the interventions to improve antibacterial prescriptions. Hence, the present prospective groundwork was conducted. MATERIALS AND METHODS: The study was conducted over the period of 6 months (April 18 to October 20, 2014). The demographics and drug use details were captured daily from patients admitted to PICU to assess World Health Organization indicators. RESULTS: A total of 200 patients enrolled, among them 119 males and 81 females. There were 12.46 (±6.16) drugs prescribed per patient, of which 2.38 (±1.48) were antibacterials. Among the total drug prescribed, 18.49% were antibacterials and 97% patients received at least one antibacterial. Ceftriaxone (49.48%) was the most commonly prescribed antibacterial, while imipenem (2.58%) and colistin (2.06%) use was very low. A total of 80.95% antibacterials were prescribed by generic name, 94.88% were administered intravenously, and 80.76% were prescribed from hospital pharmacy. The average length of PICU stay was 6.15 days (±6.20), the average length of antibacterial treatment was 6.08 days (±6.27), and the average length of empirical antibacterial treatment was 5.50 days (±5.40). The cost of antibacterial therapy per patient was Indian rupees 824.64 (±235.35). In 27 patients, bacterial culture test was positive and of whom 21 received antibacterials as per sensitivity pattern. CONCLUSIONS: The use of antibacterials was not indiscriminately high but more prescriptions per sensitivity pattern are required.

A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy.

BACKGROUND: Genetic polymorphisms in drug metabolizing enzymes (DMEs) impart distinct drug metabolizing capacity and a unique phenotype to an individual. Phenytoin has large inter-individual variability in metabolism due to polymorphisms in CYP2C9 and CYP2C19. As per Ayurveda, Prakriti imparts a unique phenotype to an individual. OBJECTIVE: To assess whether Prakriti can substitute phenotyping [therapeutic drug monitoring (TDM)] and genotyping in individualizing therapy with phenytoin in epilepsy patients. METHODS AND MATERIALS: This was a cross-sectional study conducted over a period of three years. Prakriti was assessed using standardized and validated software. Polymorphisms in CYP2C9 and CYP2C19 were assessed using Polymerase Chain Reaction (PCR)-Restriction fragment length polymorphism (PCR-RFLP). Plasma concentrations of phenytoin (phenotype) were determined using reverse phase-high performance liquid chromatography (RF-HPLC). RESULTS: Total 351 patients were enrolled for the study. Kapha vata (KV) (39%) was the predominantly observed Prakriti followed by vata kapha (VK) (20.8%) and vata pitta (VP) (8.83%) among the patients. The CYP2C9 and CYP2C19 genotype distributions were in accordance with Hardy-Weinberg equilibrium. There was no association between Prakriti and genotypes and Prakriti and phenotype (p > 0.05 each). Patients with CYP2C9 *1/*3 genotype were thrice more likely to have toxic plasma concentrations of phenytoin as compared to those with wild-type genotype (*1/*1) (Adjusted odds ratio - 3.36; 95% C.I. 1.61, 7.01). However, no such association was observed between polymorphisms of CYP2C19 and phenotype. CONCLUSIONS: We did not find any association between Prakriti and either phenotype or genotypes suggesting that Prakriti assessment would be of limited utility in individualizing phenytoin therapy in epilepsy patients.

Evaluation of cytochrome P450 2D6 phenotyping in healthy adult Western Indians.

BACKGROUND: Cytochrome P450 2D6 (CYP2D6) metabolizes around 25% of the drugs used in therapeutics and different polymorphisms have been identified in various populations. This study aimed at finding the prevalence of CYP2D6 polymorphisms using dextromethorphan as a probe drug. MATERIALS AND METHODS: Healthy participants were administered 60 mg dextromethorphan after an overnight fast and 5 ml of blood was collected 3 h postdose. A validated laboratory method was used to measure both dextromethorphan and its active metabolite, dextrorphan from plasma. Metabolic ratio (MR) of dextromethorphan to dextrorphan was calculated for each of the participants. Probit analysis was done and antimode was defined. Individuals with log MR equal to or higher than the antimode were classified as poor metabolizers (PMs) and those with values less than antimode were categorized as extensive metabolizers (EMs). RESULTS: Data from a total of 149 participants were evaluated and the median (range) of MR was 0.25 (0.03-3.01). The polynomial equation obtained in probit analysis gave an antimode for MR of 1.39. Five (3.36%) participants were PMs and 144 (96.64%) were found to be EMs. One participant had reported mild drowsiness 2 h postdose that subsided spontaneously without any intervention. CONCLUSION: The prevalence of CYP2D6 polymorphism in Western Indian population is low (3.36%) and is similar to other populations.