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Drug Load (drug + load)
Selected AbstractsThe spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewaterADDICTION, Issue 11 2009Caleb J. Banta-Green ABSTRACT Aims To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse. Design and participants Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon. Measurements Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported. Findings The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. Conclusion This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures. [source] Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsyEPILEPSIA, Issue 5 2010Maria Paola Canevini Summary Purpose:, To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods:, Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results:, Of 809 patients enrolled, 709 had localization-related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ,4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 ± 11.7 vs. 42.6 ± 11.2), and there was no correlation between AEP scores and AED load (r = ,0.05, p = 0.16). Conclusions:, AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians' intervention in individualizing treatment regimens. Taking into account the limitations of a cross-sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians' skills, than number of coprescribed AEDs and AED load. [source] Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence ReviewedEPILEPSIA, Issue 11 2000Charles L. P. Deckers Summary: Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: Thirty-nine papers were identified reporting on two-drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point. Conclusions: There is evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with an NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy. [source] Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosisJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2010H.N. Shivakumar Abstract The present study aimed to develop bilayered nail lacquer of terbinafine hydrochloride (TH) for treatment of onychomycosis. The composite nail lacquer formed an underlying drug-loaded hydrophilic layer and overlying hydrophobic vinyl layer. The hydrophilic lacquer made of hydroxylpropyl methylcellulose E-15 contained polyethylene glycol 400 (PEG 400) as a drug permeation enhancer. The vinyl lacquer was composed of poly (4-vinyl phenol) as a water-resistant film former. In vitro permeation studies in Franz diffusion cells indicated that the amount of TH permeated across the human cadaver nail in 6 days was 0.32,±,0.14, 1.12,±,0.42, and 1.42,±,0.53,µg/cm2 from control (hydrophilic lacquer devoid of PEG 400), monolayer (hydrophilic lacquer alone), and bilayered nail lacquers, respectively. A higher nail drug load was seen in vitro with the bilayered lacquer (0.59,±,0.13,µg/mg) as compared to monolayer (0.36,±,0.09,µg/mg) and control (0.28,±,0.07,µg/mg) lacquers. The drug loss despite multiple washing was significantly low (p,<,0.001) for the bilayered lacquer owing to the protective vinyl coating. Clinical studies demonstrated the efficacy of bilayered lacquer to achieve better drug load in the nail plate (1.27,±,0.184,µg/mg) compared to monolayer (0.67,±,0.18,µg/mg) and control (0.21,±,0.04,µg/mg) lacquers. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4267,4276, 2010 [source] Multivariate modeling of encapsulation and release of an ionizable drug from polymer microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Hagar I. Labouta Abstract In the formulation of polymer microspheres (MSs) loaded with verapamil hydrochloride (VRP), a low molecular weight ionizable drug, by W/O/W emulsification, the pH of the external aqueous phase proved to be a primary determinant of both IE and drug release behavior. Increasing the pH of the external aqueous phase enhanced IE (,100% at pH 8.4). This was associated with a considerable increase in initial release rate at pH 1.2. Two multivariate methods, factorial analysis (FA) and artificial neural network (ANN), were used to investigate the impact of the combined effect of the external phase pH and other parameters (polymer concentration and initial drug load) on MS characteristics; IE, initial drug release, MS size and yield. FA indicated that the external aqueous phase pH affected all responses, with a particularly strong correlation with IE in addition to a combined synergistic effect with polymer concentration on MS size. ANN showed better internal and external predictive ability of responses compared to FA. The ANN model developed in the study can be successfully used for multivariate modeling of the encapsulation and release of VRP and similar drug salts from hydrophobic polymer MSs prepared by multiple emulsification in addition to other MS characteristics. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4603,4615, 2009 [source] Antipsychotic polypharmacy at the University Psychiatric Hospital in Serbia,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2007Nevena Divac Abstract The aim of the study was to analyse the prevalence of polypharmacy with antipsychotic drugs and analyse types of coprescribing episodes at the University Psychiatric Hospital in Serbia. A sample of 120 patients (198 hospitalisations) was analysed. The prevalence of polypharmacy was calculated as the proportion of patients receiving two or more antipsychotic drugs concomitantly for at least 28 days. Total daily antipsychotic drug load was calculated as the number of defined daily doses (DDDs) of drugs per patient per day. It was compared between patients receiving monotherapy and patients receiving polypharmacy. Statistics was performed using standard statistical methods. Monotherapy was prescribed during 32.3% hospitalisations (n,=,64), while polypharmacy was noted in 67.7% (n,=,134). Polypharmacy with two drugs was observed during 126 (63.6%) hospitalisations and three antipsychotics were prescribed concomitantly during 8 (4.1%) hospitalisations. Patients' characteristics were not significantly different between patients who received only monotherapy and patients receiving polypharmacy. Patients on monotherapy had significantly more prior hospitalisations than patients from the other group (t,=,3.94, df,=,119, p,<,0.001). The prevalence of polypharmacy patient episodes (67.7%) is approximately 100% higher than the prevalence observed in developed European countries. The explanation of such prescribing habit of Serbian psychiatrists requires further investigation. The only distinguishing factor between patients receiving monotherapy and patients receiving polypharmacy is the number of prior hospitalisations. Copyright © 2007 John Wiley & Sons, Ltd. [source] The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewaterADDICTION, Issue 11 2009Caleb J. Banta-Green ABSTRACT Aims To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse. Design and participants Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon. Measurements Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported. Findings The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. Conclusion This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures. [source] | ||||||||||