Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants. Six plasma and 6 saliva PK sample collections were scheduled after a single intravenous dose of 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) was performed. Various reduced plasma sampling scenarios were evaluated by PMX simulations. Saliva and plasma samples from 25 children were included (age range, 5-70 months; weight range, 8.7-24.8 kg). Distribution of metamizole metabolites between plasma and saliva was without delay. Estimated mean (individual range) saliva/plasma fractions of 4-MAA and 4-AA were 0.32 (0.05-0.57) and 0.57 (0.25-0.70), respectively. Residual variability of 4-MAA (4-AA) in saliva was 47% (28%) versus 17% (11%) in plasma. A simplified sampling scenario with up to 6 saliva samples combined with 1 plasma sample was associated with similar PK parameter estimates as the full plasma sampling scenario. This case study with metamizole shows increased PK variability in saliva compared to plasma, compromising its suitability as single matrix for PK studies in infants. Nonetheless, rich saliva sampling can reduce the number of plasma samples required for PK characterization, thereby facilitating the conduct of PK studies to optimize dosing in pediatric patients

Ethics takes time, but not that long

© 2007 Hansson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

SalMotifDB:a tool for analyzing putative transcription factor binding sites in salmonid genomes

publishedVersio

Closing the Knowledge Gap: Hepatitis B Reactivation in Immunosuppression

Background&#x0D; The usage of immunosuppressive medications (ISMs), and specifically disease modifying anti-rheumatic drugs (DMARDs), in a wide range of internal medicine subspecialties has increased the risk of hepatitis B virus re-activation (HBVr). We assessed the understanding of HBVr using a Canada-wide survey.&#x0D; Methods&#x0D; An electronic survey was sent to 521 members of the Canadian Rheumatology Association (CRA). The questions focused on the knowledge of screening, monitoring and management of patients with chronic or past infection with HBV in the setting of starting ISMs.The results were compared to the American Gastroenterology Association (AGA) guidelines. &#x0D; Results&#x0D; A total of142 respondents were included in the analysis (response rate = 27.3%). Over 50% of the respondents would order unnecessary tests such as anti-HBs or anti-HBc for monitoring a HBsAg positive patient on an ISMs. There were 43% of responders who answered incorrectly to starting anti-viral prophylaxis for HBsAg positive patients on synthetic DMARDs (sDMARDs).&#x0D; Conclusion&#x0D; There are some knowledge gaps amongst physicians managing rheumatology patients with chronic or past infection with HBV in the setting of ISMs. The AGA guidelines were summarized and incorporated into a user-friendly guide.</jats:p