New Guidance on Cytochrome P450 2C19 Phenotype-based Use of Proton Pump Inhibitors.

ABSTRACT: Since the approval of the first proton pump inhibitor (PPI) in 1989, our knowledge regarding this class of medications has further developed. An increasing amount of data now supports the association between cytochrome P450 2C19 (CYP2C19) phenotype and PPI safety and efficacy. This includes pediatric studies, such as those published here and in other pediatric journals within the past year. Moreover, the most recent pediatric Helicobacter pylori guidelines stated that using the PPIs that are less dependent on CYP2C19 for inactivation may be preferred for H pylori eradication among populations that are more likely to have rapid clearance of CYP2C19-metabolized PPIs. Conversely, pantoprazole package insert recommends a dose reduction in known pediatric CYP2C19 poor metabolizers (PMs), citing a 6-fold increase in serum concentrations compared with normal metabolizers (NMs). The purpose of this communication is to introduce a recently published Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and PPI dosing.

The impact of new guidelines on the prevalence of hypertension in children: A cross-sectional evaluation.

Updated clinical practice guidelines for screening blood pressures in pediatric patients were published in 2017. They differ from the previous guideline, known as the Fourth Report, providing updated population normal values and blood pressure categorization. We hypothesized that the prevalence of abnormal blood pressure in children and adolescents would be higher using the new clinical practice guidelines. We present a cross-sectional study of screening blood pressure values for children 3 to 18 years of age obtained during well-child visits at a primary care clinic. All blood pressure values were categorized using both the Fourth Report and the Clinical Practice Guideline. A total of 2635 blood pressure measurements were extracted, and 2600 were eligible for analysis. Using the clinical practice guideline, the prevalence of hypertension increased to 17.85% compared to 9.5% per the Fourth Report (P < 0.0001). Of those patients classified as having a normal blood pressure by the Fourth Report, 12% changed to abnormal when applying the Clinical Practice Guideline. All subgroups had a significant increase in the prevalence of abnormal blood pressure. The most dramatic increase in the prevalence of stage 1 and stage 2 hypertension was seen in six patient subgroups: males, 3-12 years of age, Hispanic ethnicity, race designated as other, normal weight, and overweight. Applying the new Clinical Practice Guideline increased the prevalence of elevated blood pressure and stage 1 and stage 2 hypertension in children and adolescents, requiring more follow-up and intervention than previously expected for this patient population.

Technology for Augmenting Type 1 Diabetes Mellitus Management.

Type 1 diabetes mellitus has witnessed significant progress in its management over the past several decades. This review highlights technologic advancements in type 1 diabetes management. Continuous glucose monitoring systems are now available at various functionality and cost levels, addressing diverse patient needs, including a recently US Food and Drug Administration (FDA)-approved implantable continuous glucose monitoring system (CGMS). Another dimension to these state-of-the-art technologies is CGMS and insulin pump integration. These integrations have allowed for CGMS-based adjustments to basal insulin delivery rates and suspension of insulin delivery when a low blood glucose event is predicted. This review also includes a brief discussion of upcoming technologies such as patch-based CGMS and insulin-glucagon dual-hormonal delivery.

Evolving Pharmacotherapeutic Strategies for Type 1 Diabetes Mellitus.

Despite pharmacotherapeutic advancements in the management of type 1 diabetes mellitus during the past several decades, patients struggle to achieve glycemic goals. Additionally, hypoglycemia, especially in extremes of age, decreases quality of life. The lack of optimal glycemic control and risk for hypoglycemia are multifactorial. Nevertheless, endeavors aiming to develop pharmacotherapeutic options with enhanced pharmacokinetic, pharmacodynamic, and clinical profiles continue. This review article discusses recent ventures in 3 categories of insulin, non-insulin, and glucagon products.

Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities.

Cytochrome P450 (CYP) enzyme 2B6 plays a significant role in the stereo-selective metabolism of (S)-methadone to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine, an inactive methadone metabolite. Elevated (S)-methadone can cause cardiotoxicity by prolonging the QT interval of the heart's electrical cycle. Large inter-individual variability of methadone pharmacokinetics causes discordance in the relationship between dose, plasma concentrations and side effects. The purpose of this study was to determine if one or more single nucleotide polymorphisms (SNPs) located within the CYP2B6 gene contributes to a poor metabolizer phenotype for methadone in these fatal cases. The genetic analysis was conducted on 125 Caucasian methadone-only fatalities obtained from the West Virginia and Kentucky Offices of the Chief Medical Examiner. The frequency of eight exonic and intronic SNPs (rs2279344, rs3211371, rs3745274, rs4803419, rs8192709, rs8192719, rs12721655 and rs35979566) was determined. The frequencies of SNPs rs3745274 (*9, c516G > T, Q172H), and rs8192719 (21563 C > T) were enhanced in the methadone-only group. Higher blood methadone concentrations were observed in individuals who were genotyped homozygous for SNP rs3211371 (*5, c1459C > T, R487C). These results indicate that these three CYP2B6 SNPs are associated with methadone fatalities.