Population Pharmacokinetics of Colistin Methanesulfonate Sodium and Colistin in Critically Ill Patients: A Systematic Review.

Understanding the pharmacokinetics parameter of colistin methanesulfonate sodium (CMS) and colistin is needed to optimize the dosage regimen in critically ill patients. However, there is a scarcity of pharmacokinetics parameters in this population. This review provides a comprehensive understanding of CMS and colistin pharmacokinetics parameters in this population. The relevant studies published in English that reported on the pharmacokinetics of CMS and colistin from 2000 until 2020 were systematically searched using the PubMed and Scopus electronic databases. Reference lists of articles were reviewed to identify additional studies. A total of 252 citation titles were identified, of which 101 potentially relevant abstracts were screened, and 25 full-text articles were selected for detailed analysis. Of those, 15 studies were included for the review. This review has demonstrated vast inter-study discrepancies in colistin plasma concentration and the pharmacokinetics parameter estimates. The discrepancies might be due to complex pathophysiological changes in the population studied, differences in CMS brand used, methodology, and study protocol. Application of loading dose of CMS and an additional dose of CMS after dialysis session was recommended by some studies. In view of inter-patient and intra-patient variability in colistin plasma concentration and pharmacokinetics parameters, personalized colistin dosing for this population is recommended.

Relationship Between Adherence to Opioid Analgesics and Pain Beliefs Among Patients with Cancer Pain at Tertiary Care Hospitals in Malaysia.

CONTEXT: Pain is a common and distressing symptom among cancer patients. Opioid analgesics are the mainstay of cancer pain management, and adequate adherence plays an important role in achieving good pain control. PURPOSE: To determine the level of adherence to opioid analgesics in patients with cancer pain and to identify factors that may influence the adherence. PATIENT AND METHODS: This was a cross-sectional study conducted from March to June 2018 at two tertiary care hospitals in Malaysia. Study instruments consisted of a set of validated questionnaires; the Medication Compliance Questionnaire, Brief Pain Inventory and Pain Opioid Analgesic Beliefs─Cancer scale. RESULTS: A total of 134 patients participated in this study. The patients' adherence scores ranged from 52-100%. Factors with a moderate, statistically significant negative correlation with adherence were negative effect beliefs (rs= -0.53, p<0.001), pain endurance beliefs (rs = -0.49, p<0.001) and the use of aqueous morphine (rs = -0.26, p=0.002). A multiple linear regression model on these predictors resulted in a final model which accounted for 47.0% of the total variance in adherence (R2 = 0.47, F (7, 126) = 15.75, p<0.001). After controlling for other variables, negative effect beliefs were the strongest contributor to the model (ß = -0.39, p<0.001) and uniquely explained 12.3% of the total variance. CONCLUSION: The overall adherence to opioid analgesics among Malaysian patients with cancer pain was good. Negative effects beliefs regarding cancer pain and opioids strongly predicted adherence.

An integrated linkage map of interspecific backcross 2 (BC2) populations reveals QTLs associated with fatty acid composition and vegetative parameters influencing compactness in oil palm.

BACKGROUND: Molecular breeding has opened new avenues for crop improvement with the potential for faster progress. As oil palm is the major producer of vegetable oil in the world, its improvement, such as developing compact planting materials and altering its oils' fatty acid composition for wider application, is important. RESULTS: This study sought to identify the QTLs associated with fatty acid composition and vegetative traits for compactness in the crop. It integrated two interspecific backcross two (BC2) mapping populations to improve the genetic resolution and evaluate the consistency of the QTLs identified. A total 1963 markers (1814 SNPs and 149 SSRs) spanning a total map length of 1793 cM were integrated into a consensus map. For the first time, some QTLs associated with vegetative parameters and carotene content were identified in interspecific hybrids, apart from those associated with fatty acid composition. The analysis identified 8, 3 and 8 genomic loci significantly associated with fatty acids, carotene content and compactness, respectively. CONCLUSIONS: Major genomic region influencing the traits for compactness and fatty acid composition was identified in the same chromosomal region in the two populations using two methods for QTL detection. Several significant loci influencing compactness, carotene content and FAC were common to both populations, while others were specific to particular genetic backgrounds. It is hoped that the QTLs identified will be useful tools for marker-assisted selection and accelerate the identification of desirable genotypes for breeding.

Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach.

AIMS: Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor approved and is widely used in combination therapy to treat HIV-1 infection. The pharmacokinetics of nevirapine was extensively studied in various populations with a parametric approach. Hence, this study was aimed to determine population pharmacokinetic parameters in Malaysian HIV-infected patients with a non-parametric approach which allows detection of outliers or non-normal distribution contrary to the parametric approach. METHODS: Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters' estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC. RESULTS: The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC. CONCLUSIONS: In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.

Exploring CYP2B6 activity by measuring the presence ofnevirapine hydroxy metabolites in plasma.

BACKGROUND/AIM: Nevirapine is a reverse-transcriptase inhibitor widely used in combination therapy to treat HIV infection. Nevirapine is extensively metabolized in the liver and CYP2B6 is mainly responsible for oxidation of 3-hydroxynevirapine (3-OH NVP). This study aims to explore CYP2B6 activity by measuring 2-hydroxynevirapine (2-OH NVP) and 3-OH NVP in plasma and to identify factors associated with nevirapine pharmacokinetic parameters. MATERIALS AND METHODS: A total of 112 patients were recruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction. RESULTS: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters. CONCLUSION: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.

Implementation of a new procedure: laparoscopic versus robotic sacrocolpopexy.

PURPOSE: The purpose of this study was to compare the implementation process and the learning curves of laparoscopic and robotic-assisted laparoscopic sacrocolpopexy (LSC and RSC, respectively) for vaginal apex prolapse. METHODS: A retrospective study of the first 40 LSC and first 40 RSC procedures performed at one medical center. The primary outcomes were intraoperative bleeding, operative time, and hospitalization. Secondary outcomes were surgical complications. The independent t test, paired t test, χ(2) test, Fisher's exact test and Pearson's correlation were used to analyze the data. We assumed that 34 participants were needed in each group to detect a 50 ml or more difference in estimated blood loss between laparoscopic and robotic surgeries, MAIN RESULTS: Age, preoperative pelvic organ prolapse quantification (POPQ) staging, and concomitant medical disorders did not differ significantly by procedure type. For LSC and RSC, the mean estimated intraoperative blood loss was 206 ± 107 and 48 ± 55 ml, P < 0.0001; mean operative times were 176 (110-380 min) and 186 (105-345 min), P = 0.34; and mean length of hospital stay, 3.8 ± 1 and 2.4 ± 1 days, P < 0.0001, respectively. Adverse events were rare, not severe, and did not differ significantly by procedure type. CONCLUSIONS: RSC and LSC are feasible procedures with acceptable complication rates. RSC enables operating more anatomically with less bleeding.