A new accurate method for predicting lithium clearance and daily dosage requirements in adult psychiatric patients

Objective: The present study aimed to derive new equations for estimating lithium clearance and daily dosage requirements needed to achieve an intended lithium serum level for adult psychiatric inpatients and outpatients. Methods: Data were retrospectively collected from 60 adult psychiatric patients (34 males and 26 females, aged between 18-80 years) in both inpatient and outpatient settings. All variables that might affect lithium clearance and/or lithium serum concentration were included and analyzed by stepwise multiple linear regression to produce equations describing lithium clearance and daily dosage requirements for these patients. The validation of the developed equations was performed by application to another 60 psychiatric subjects in both the inpatient and outpatient settings. The bias and accuracy of the new methods were also compared to those set forth by the empirical method and the a priori methods developed by Zetin, Pepin, Jermain and Terao and colleagues. Results: The following prediction equations for lithium clearance (CLLi) were obtained: CLLi (inpatients) = 0.932 + 0.185CL(Cr) and CLLi (outpatients) = 1.021 + 0.141CL(Cr). The equations derived for daily dosage requirements were: daily dose (inpatients, mg) = 350.15 + 289.92 (desired lithium level, mmol/L) + 0.84 (weight, kg) - 1.76 (age, years) + 34.43 [tricyclic antidepressant (TCA), yes = 1, no = 0] + 62.1(CLCr, L/h) + 13.1 [blood urea nitrogen (BUN), mmol/L] + 40.9 (sex, male = 1, female = 0) and daily dose (outpatients, mg) = 784.92 + 530.22 (desired lithium level, mmol/L) + 8.61 (weight, kg) - 12.09 (age, years) - 11.14 (TCA, yes = 1, no = 0) - 7.63 (CLCr, L/h) - 42.62 (BUN, mmol/L) - 23.43 (sex, male = 1, female = 0). In the present method, the prediction error for clearance was 10.31% and 6.62% for inpatients and outpatients, respectively, and the prediction error for daily dosage requirements was 3.96% and 2.95% for inpatients and outpatients, respectively. Conclusions: Compared to previously reported methods, the present method proved to be accurate and can be safely used for the prediction of lithium clearance and daily dosage requirements in psychiatric inpatients and outpatients

Influence of piperacillin on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate studies

The influence of concomitant administration of piperacillin (PIP) on the pharmacokinetic parameters of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) was studied in rabbits. Six rabbits received an initial i.v. bolus (0.21 mg kg(-1)) followed by a constant-rate i.v infusion of the drug (5 mu g min(-1) kg-(1)) for 240 min. The PIP dose (30 mg kg(-1)) was repeated every 30 min until the end of the infusion period. The control group consisted of four rabbits treated the same way except for the addition of PIP. There were significant increases in the mean residence times found for MTX (MRTinf) and 7-OH-MTX (MRTm,inf) following PIP administration. Concomitant administration of PIP with MTX also produced significant 1.5- and 2.8-fold increases in the area under the curve of MTX and 7-OH-MTX, respectively. The total body clearance of MTX and the operative total body clearance of 7-OH-MTX significantly decreased, but in a less than proportional manner. The study demonstrates that the interaction between MTX and PIP is mainly due to the reduced clearance of both MTX and 7-OH-MTX combined with a slight increase in the formation clearance of the metabolite

Liquid chromatographic assay of abouthiouzine in plasma and its application to pharmacokinetic studies

Abouthiouzine is a newly synthesized antithyroid agent with a proposed less adverse effects profile than other currently used drugs. A simple and rapid reversed phase high performance liquid chromatography assay was developed to determine the concentration of abouthiouzine in human plasma. The procedure involved extraction of the drug and propranolol (internal standard) from the plasma using ethylacetate. The extract was evaporated under nitrogen and the residue was constituted with the mobile phase and injected onto mu-Bondapack phenyl column (10 mum, 3.9 mm x 150 mm). The mobile phase consisted of 10 mM potassium dihydrogen phosphate buffer, acetonitrile, and methanol in the ratio of 60:25:15 (v/v/v, pH = 3.0), which was delivered at a rate of 1.5 ml/min. Abouthiouzine and the internal standard were monitored using UV detection at 240 nm; the run time was less than 5 min. The detection limit of abouthiouzine is 0.5 mug/ml. The within- and between-day coefficients of variation were less than 7%. Our method has been successfully used to measure abouthiouzine plasma concentrations in a rabbit model following an intravenous administration of the drug. (C) 2004 Elsevier B.V All rights reserve

Medicine storage, wastage, and associated determinants among urban households : a systematic review and meta-analysis of household surveys

Background: Irrational household storage of medicines is a world-wide problem, which triggers medicine wastage as well as its associated harms. This study aimed to include all available evidences from literature to perform a focused examination of the prevalence and factors associated with medicine storage and wastage among urban households. This systematic review and meta-analysis mapped the existing literature on the burden, outcomes, and affective socio-economic factors of medicine storage among urban households. In addition, this study estimated pooled effect sizes for storage and wastage rates. Methods: Household surveys evaluating modality, size, costs, and affective factors of medicines storage at home were searched in PubMed, EMBASE, OVID, SCOPUS, ProQuest, and Google scholar databases in 2019. Random effect meta-analysis and subgroup analysis were used to pool effect sizes for medicine storage and wastage prevalence among different geographical regions. Results: From the 2604 initial records, 20 studies were selected for systematic review and 16 articles were selected for meta-analysis. An overall pooled-prevalence of medicine storage and real wastage rate was 77 and 15%, respectively. In this regard, some significant differences were observed between geographical regions. Southwest Asia region had the highest storage and wastage rates. The most common classes of medicines found in households belonged to the Infective agents for systemic (17.4%) and the Nervous system (16.4%). Moreover, income, education, age, the presence of chronic illness, female gender, and insurance coverage were found to be associated with higher home storage. The most commonly used method of disposal was throwing them in the garbage. Conclusions: Factors beyond medical needs were also found to be associated with medicine storage, which urges effective strategies in the supply and demand side of the medicine consumption chain. The first necessary step to mitigate home storage is establishing an adequate legislation and strict enforcement of regulations on dispensing, prescription, and marketing of medicines. Patient’s pressure on excessive prescription, irrational storage, and use of medicines deserve efficient community-centered programs, in order to increase awareness on these issues. So, hazardous consequences of inappropriate disposal should be mitigated by different take back programs, particularly in low and middle income countries.