Niosomes are reported to increase the skin permeation and bioavailability of topically applied drug molecules. However, very few studies were reported for nanometer-sized niosome vesicles. The aim of the present study was to prepare minoxidil-loaded niosomal formulation using ethanol injection method. Surfactant screening showed that only Span 60, Span 20, and Tween 20 with cholesterol have capability of nano size vesicle formation. The formed niosomes were characterized for entrapment efficiency, vesicle size, scanning electron microscope, and physical stability. By modulation of surfactant and cholesterol ratio maximum entrapment up to 34.70 ± 1.1 % with size of 470 ± 27 nm was obtained (Span 60/cholesterol ratio of 1:2). The vesicle size obtained was between 150 and 800 nm that was depending on cholesterol ratio and type of nonionic surfactant employed. The in vitro skin permeation study showed that an increase in cholesterol concentration in niosome vesicles increases minoxidil skin retention. Niosome formulation prepared with 1:2 ratio of Span 60 and cholesterol showed 17.21 ± 3.2 % skin retention of minoxidil, which is more than eightfold as compared to control minoxidil gel.

Aims and objectivesVancomycin 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 methodsTwelve 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).ResultsThe steady-state mean Cssmax was 40.94 μg/mL (±15.07), and mean AUC0–8 hours was 124.15 μg/mL (±51.27). The mean t1/2 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.ConclusionThe 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 articleMali 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.

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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.

BackgroundGenetic 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.ObjectiveTo assess whether Prakriti can substitute phenotyping [therapeutic drug monitoring (TDM)] and genotyping in individualizing therapy with phenytoin in epilepsy patients.Methods and materialsThis 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).ResultsTotal 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.ConclusionsWe 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.

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.

Rationale:Antibacterials are largely prescribed to the intensive care unit (ICU) patients due to high prevalence of infections. However, appropriate use of antibacterials is imperative; since the misuse of antibacterials increases antibacterial resistance and ultimately, it has negative impact on health care and economic system. Hence, continuous antibacterials prescription assessments are very important to judge and improve prescription patterns. The present work was carried out at public and private hospitals to assess the differences in antibacterial prescribing pattern.Methods:The present study was conducted at three public and two private hospitals over the period of 14 months. Demographic and drug use details were captured daily from patients admitted to medical ICUs to assess the World Health Organization indicators.Results:A total of 700 patients were enrolled across the five centers (140 per center), among them 424 were male and 276 were female. Average number of drugs and antibacterials prescribed at public hospitals are significantly higher than the private hospital. However, percentage of antibacterial agents prescribed at public hospitals was significantly lower than the private hospitals (P = 0.0381). Private hospitals had significantly lower percentage of antibacterial agents prescribed by generic name (P < 0.0001). Differences in change of antibacterial agents required were not statistically significantly different (P = 0.1888); however, significant difference was observed in percentage of patients who received antibacterial treatment as per sensitivity pattern (P = 0.0385) between public and private hospitals. Significantly higher mortality was observed in public hospitals compared to private hospitals (<0.0001).Conclusions:More generic prescriptions and more number of prescriptions as per the sensitivity pattern are required at each public and private hospital.

Abstract. The aim of the present study was to formulate serratiopeptidase (SER)-loaded chitosan (CS) nanoparticles for oral delivery. SER is a proteolytic enzyme which is very sensitive to change in temperature and pH. SER-loaded CS nanoparticles were fabricated by ionic gelation method using tripolyphosphate (TPP). Nanoparticles were characterized for its particle size, morphology, entrapment efficiency, loading efficiency, percent recovery, and in vitro dissolution study. SER-CS nanoparticles had a particle size in the range of 400-600 nm with polydispersity index below 0.5. SER association was up to 80 ±4.2%. SER loading and CS/TPP mass ratio were the primary parameters having direct influence on SER-CS nanoparticles. SER-CS nanoparticles were freeze dried using trehalose (20%) as a cryoprotectant. In vitro dissolution showed initial burst followed by sustained release up to 24 h. In vivo antiinflammatory activity was carried out in rat paw edema model. In vivo anti-inflammatory activity in rat paw edema showed prolonged anti-inflammatory effect up to 32 h relative to plain SER.