Bioequivalence of a Generic Nateglinide Formulation in Healthy Chinese Volunteers under Fasting and Fed Conditions: A Randomized, Open-Label, Double-Cycle, Double-Crossover Study.

INTRODUCTION: Nateglinide or N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine is a drug with a rapid hypoglycemic effect that is mainly used in the treatment of type 2 diabetes. Very few studies have assessed bioequivalence based on feeding status. This study aimed to assess the pharmacokinetic bioequivalence and safety of nateglinide-containing tablets (0.12 g) in healthy Chinese volunteers under fasting and fed conditions. METHODS: The studies were performed in 2017-2018 in the Phase I Clinical Trial Ward of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China. Eligible Chinese volunteers received a single 0.12-g dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. Blood samples were collected at various time intervals, and plasma nateglinide concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Then, the adverse events, laboratory test results, vital signs, and physical exam findings were compared between the 2 groups. RESULTS: The ratios of the geometric means of Cmax, AUC0-t, and AUC0-inf of the tested to reference preparations under fasting conditions were 105.03% (90% confidence interval [CI]: 99.53-110.83%), 104.02% (90% CI: 101.37-106.74%), and 104.04% (90% CI: 101.38-106.77%), respectively. The same ratios under fed conditions were 96.55% (90% CI: 85.80-108.65%), 103.08% (90% CI: 100.07-106.18%), and 103.07% (90% CI: 100.21-106.01%), respectively. The 90% CI values for Cmax, AUC0-t, and AUC0-inf fell within the accepted range of bioequivalence (80.00-125.0%). Common adverse events included hypoglycemia, heart rate increase, palpitation, sweating, dizziness, and diarrhea. CONCLUSIONS: The test formulation (0.12 g) met the CFDA's regulatory definition for bioequivalence to the reference formulation. Both formulations were well tolerated by healthy Chinese subjects. TRIAL REGISTRATION: This trial has been registered in the Chinese Clinical trial registry (ChiCTR2000030694), March 10, 2020.

Bioequivalence of topical generic products. Part 1: Where are we now?

Regulatory accepted methods for bioequivalence assessment of topical generic products generally involve long and expensive clinical endpoint studies. The only alternative relies on pharmacodynamic trials, solely applicable to corticosteroids. Considerable efforts have been channeled towards the development and validation of other analytical surrogates. The majority of these alternative methods rely on in vitro methodologies that allow a more sensitive and reproducible bioequivalence assessment, avoiding at the same time the financial burden that deeply characterizes clinical trials. The development and validation of these methods represent interesting areas of opportunities for generic drugs, since by enabling faster submission and approval processes, an enlargement of topical drug products with generic version is more easily attainable. This review aims to present a critical discussion of the most promising alternative methods, with particular emphasis on in vitro permeation studies and near infrared spectroscopy studies. Since the last technique is not broadly forecast as a bioequivalence assessment tool, its suitability is assessed by a careful analysis of patents that claim the use of NIR radiation in the skin. In fact, the extensive coverage of the devices that use this technology highlights its applicability towards a better understanding of the mechanism underlying topical drug delivery.

Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma.

PURPOSE: To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study. DESIGN: Database study. PARTICIPANTS: In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence. METHODS: Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed. MAIN OUTCOME MEASURES: Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG. RESULTS: The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P = 1.0 × 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P = 1.2 × 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P = 1.8 × 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P = 5.9 × 10-10). CONCLUSIONS: We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.

Economic evaluation of weekends-off antiretroviral therapy for young people in 11 countries.

OBJECTIVES: To analyze the cost effectiveness of short-cycle therapy (SCT), where patients take antiretroviral (ARV) drugs 5 consecutive days a week and have 2 days off, as an alternative to continuous ARV therapy for young people infected with human immunodeficiency virus (HIV) and taking efavirenz-based first-line ARV drugs. METHODS: We conduct a hierarchical cost-effectiveness analysis based on data on clinical outcomes and resource use from the BREATHER trial. BREATHER is a randomized trial investigating the effectiveness of SCT and continuous therapy in 199 participants aged 8 to 24 years and taking efavirenz-based first-line ARV drugs in 11 countries worldwide. Alongside nationally representative unit costs/prices, these data were used to estimate costs and quality adjusted life years (QALYs). An incremental cost-effectiveness comparison was performed using a multilevel bivariate regression approach for total costs and QALYs. Further analyses explored cost-effectiveness in low- and middle-income countries with access to low-cost generic ARV drugs and high-income countries purchasing branded ARV drugs, respectively. RESULTS: At 48 weeks, SCT offered significant total cost savings over continuous therapy of US dollar (USD) 41 per patient in countries using generic drugs and USD 4346 per patient in countries using branded ARV drugs, while accruing nonsignificant total health benefits of 0.008 and 0.009 QALYs, respectively. Cost-effectiveness estimates were similar across settings with access to generic ARV drugs but showed significant variation among high-income countries where branded ARV drugs are purchased. CONCLUSION: SCT is a cost-effective treatment alternative to continuous therapy for young people infected with HIV in countries where viral load monitoring is available.

Likelihood approach for evaluating bioequivalence of highly variable drugs.

Bioequivalence (BE) is required for approving a generic drug. The two one-sided tests procedure (TOST, or the 90% confidence interval approach) has been used as the mainstream methodology to test average BE (ABE) on pharmacokinetic parameters such as the area under the blood concentration-time curve and the peak concentration. However, for highly variable drugs (%CV > 30%), it is difficult to demonstrate ABE in a standard cross-over study with the typical number of subjects using the TOST because of lack of power. Recently, the US Food and Drug Administration and the European Medicines Agency recommended similar but not identical reference-scaled average BE (RSABE) approaches to address this issue. Although the power is improved, the new approaches may not guarantee a high level of confidence for the true difference between two drugs at the ABE boundaries. It is also difficult for these approaches to address the issues of population BE (PBE) and individual BE (IBE). We advocate the use of a likelihood approach for representing and interpreting BE data as evidence. Using example data from a full replicate 2 × 4 cross-over study, we demonstrate how to present evidence using the profile likelihoods for the mean difference and standard deviation ratios of the two drugs for the pharmacokinetic parameters. With this approach, we present evidence for PBE and IBE as well as ABE within a unified framework. Our simulations show that the operating characteristics of the proposed likelihood approach are comparable with the RSABE approaches when the same criteria are applied.

Bioavailability and stability of intravenous iron sucrose originator versus generic iron sucrose AZAD.

CONTEXT: Severe iron deficiency requires intravenous iron supplementation to replenish iron stores. Intravenous iron sucrose has been used for decades for the treatment of anemia. New generic iron sucrose products are now marketed for the use in several countries and there is an ongoing discussion about the safety and efficacy of iron sucrose similars. OBJECTIVE: In this study, we compared the iron sucrose originator Venofer® and the generic iron sucrose AZAD (ISA) regarding bioavailability, toxicity and stability in human THP-1 cells and HepG2 cells. METHODS: The bioavailability of Venofer® and ISA was investigated in both cell types by a ferrozin-based assay. The release of incorporated iron was assayed by atomic absorption spectroscopy. Ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to investigate the intracellular labile iron pool (LIP), which was measured by the fluorescent calcein assay. The amount of redox-active iron within the iron formulations was assayed using fluorescent dichlorofluorescein. RESULTS: We found no significant differences in all parameters between Venofer® and ISA in regard of bioavailability, toxicity and stability in vitro. DISCUSSION: ISA shows identical physico-chemical features and identical bioavailability in vitro. This study is a profound basis for future clinical tests with generic iron sucrose compounds.

Comparison of scaled-average, population, and individual bioequivalence on 2 tablets of pitavastatin calcium: a 3-period, reference-replicated, crossover study in healthy Chinese volunteers.

BACKGROUND: Pitavastatin, a fully synthetic ß-hydroxy-ß-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject variability and interchangeability of this newly developed generic product and the branded innovator product have rarely been investigated in the Chinese population. PURPOSE: The aim of this study is to develop and compare the scaled-average, population, and individual bioequivalence (BE) of pitavastatin calcium tablets in healthy Chinese volunteers. This study will be used to allow for the interchangeability (switchability and prescribability) of the 2 products in clinical medication in China. METHODS: A single-dose, reference-replicated, 3-period crossover BE study was conducted in 36 healthy male volunteers. Plasma samples were collected before and after oral administration of 2-mg test or reference tablets. A LC-MS/MS method was used to determine the concentration of pitavastatin calcium. A noncompartmental method was used to investigate the pharmacokinetic parameters. The ANOVA and 90% CIs of ln(AUC0-t) and ln(Cmax) were used for statistical analysis of scaled-average BE. A nonparametric test (Wilcoxon signed rank test) was performed to Tmax. The analyses of population BE and individual BE were used to assess the switchability and prescribability of the 2 products. FINDINGS: Thirty-six volunteers were enrolled in this clinical research; 33 volunteers completed the 3 treatment periods. The mean (SD) relative bioavailability calculated from the ratios (T/R) of AUC0-t was 101.3% (19.7%). The mean ln(AUC0-t) and ln(Cmax) were 98.64 (90% CI, 93.44-104.13) and 98.68 (90% CI, 91.88-105.99) within previously stipulated ranges recommended by the US Food and Drug Administration and the China Food and Drug Administration (CFDA). The intrasubject %CVs of AUC0-t and Cmax were 12.0% and 18.0% for the reference tablet and 13.0% and 17.0% for the test tablet. No significant differences were found among Tmax (0.742 ± 0.276, 0.674 ± 0.202, and 0.689 ± 0.226, respectively) for reference tablet 1, reference Supplemental Table II in the online version at 10.1016/j.clinthera.2014.06.21, and test tablet by a Wilcoxon test (P > 0.05). For ln(AUC0-t) and ln(Cmax), the statistical test-reference ratios were 99.13% and 98.95%, respectively. After inspecting the results for reference and mixed scaling, all the upper confidence limits were <0; therefore, population and individual BE were given. IMPLICATIONS: In the healthy Chinese males, the generic and branded name tablets of pitavastatin calcium are bioequivalent at the rate and extent of absorption after a comparison of scaled-average, population, and individual BE and thus may be used interchangeably. Both the formulations are generally well tolerated. Chinese Clinical Trial identifier: ChiCTR-TTRCC-13003973.

[Generic drugs and the consumption trends of antihypertensives in Morocco]. / Les médicaments génériques et l'évolution de la consommation des antihypertenseurs au Maroc.

BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population.

Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

BACKGROUND: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. METHODS AND RESULTS: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. CONCLUSION: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

OBJECTIVE: Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. METHODS: In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. RESULTS: Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. CONCLUSIONS: A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Test non-inferiority and sample size determination based on the odds ratio under a cluster randomized trial with noncompliance.

Because the odds ratio (OR) possesses certain desirable statistical properties, the OR has been recommended elsewhere to measure the relative treatment effect in establishing non-inferiority. For cost efficiency, we may often employ a cluster randomized trial (CRT), in which randomized units are clusters of patients. Furthermore, it is not uncommon to encounter data in which there are patients not complying with their assigned treatment. Under the Dirichlet multinomial model, we have developed a test statistic for assessing non-inferiority based on the OR between two treatments under a CRT with noncompliance. We have further derived a sample size formula accounting for both noncompliance and the intraclass correlation for a desired power 1 - ß of detecting non-inferiority with respect to the OR at a nominal α level. Using Monte Carlo simulation, we have evaluated the performance of the proposed test statistic and sample size formula. Finally, we use the CRT studying the effect of vitamin A supplementation on mortality among preschool children to illustrate the use of the sample size formula given here.

The impact of generic reference pricing interventions in the statin market.

OBJECTIVES: The objective of this study was to evaluate the intended and unintended impact on pharmaceutical use and sales of three public reimbursement reforms applied to the prescription of statins: a Spanish generic reference pricing system, and two competing policies introduced by the Andalusian Public Health Service. METHODS: This study is designed as an interrupted time series analysis with comparison series of 46 monthly drug use and sales figures from January 2001 to October 2004 for each active ingredient. RESULTS: The mean monthly saving for the year after the introduction of reference pricing was 16.7% of total lovastatin sales, representing only 1.1% of total statins sales. Mean monthly savings for the 10 months after reference pricing being applied to simvastatin were 51.8% of simvastatin sales, and 13.9% of statin sales. Over the 46 months of the study, all analysed public interventions resulted in a 2.2% average monthly decrease in statin sales in the rest of Spain and savings non-significantly different from zero in Andalusia. CONCLUSION: RP has been effective at reducing the volume of sales growth of the off-patent statins, yet its overall impact on sales of all statins has been relatively modest.

Cost-effectiveness of high-dose atorvastatin compared with regular dose simvastatin.

AIMS: The aim of the study was to evaluate the long-term cost-effectiveness of high-dose atorvastatin when compared with generic simvastatin for secondary prevention in Denmark, Finland, Norway, and Sweden based on the recently completed IDEAL trial. METHODS AND RESULTS: The IDEAL trial showed that high-dose treatment with atorvastatin was associated with fewer non-fatal myocardial infarctions (MI) or coronary heart disease death (RR 0.89; 95% CI 0.78-1.01) and major cardiovascular events by (RR 0.87; 95% CI 0.77-0.98) or any coronary event (RR 0.84; 95% CI 0.76-0.91) than simvastatin with no significant difference in the number of serious adverse events. Costs during the trial period was estimated based on the trial data and a Markov model was constructed where the risk of MIs and revascularization procedures and the long-term costs, quality of life, and mortality associated with these events was simulated. Costs were based on resource consumptions recorded in the trial multiplied with recent unit costs from each country. Both direct health care costs and indirect costs (costs from lost production due to work absence) were included. Intervention lasted for the duration of the trial (4.8 years) while health-effects and costs are predicted for the lifespan of the patient. The main outcome was quality adjusted life-years (QALY) gained. High-dose treatment was predicted to lead to a mean increase in survival of 0.049 years per patient and 0.033 QALYs gained. The cost to gain one QALY was predicted to 47,197euro (Denmark), 62,639euro (Finland), 35,210euro (Norway), and 43,667euro (Sweden), with cost-effectiveness ratio decreasing with higher risk. CONCLUSION: In the prevention of cardiovascular events among patients with a previous MI, high-dose atorvastatin appears to be a cost-effective strategy when compared with generic simvastatin 20-40 mg in Denmark, Norway, and Sweden. In Finland, it is cost-effective in high-risk patients. The key driver of the cost-effectiveness is the price-difference between 80 mg atorvastatin and generic simvastatin.

Utilization and drug cost outcomes of a step-therapy edit for generic antidepressants in an HMO in an integrated health system.

OBJECTIVE: Antidepressants do not differ significantly in their ability to treat depression. Excluding the tricyclic antidepressants (TCAs), these drugs also do not differ significantly in their incidence of adverse events. Therefore, the initial choice of antidepressant medication should be based, in part, on cost. The objective of this study was to evaluate the impact on utilization and costs of a generic steptherapy edit for antidepressant drugs excluding TCAs in a health maintenance organization (HMO) in an integrated health system (IHS). METHODS: The pharmacy department of the 440,000-member HMO in an IHS collaborated with the Behavioral Health Clinical Program to design an intervention that required generic antidepressants as first-line pharmacotherapy. Under the GenericStart! Program, a brand-name antidepressant was covered only after trial with a generic antidepressant, excluding TCAs. A step-therapy edit was added to the pharmacy claims processing system on January 1, 2005. All new starts, defined as members with no claims history of antidepressant treatment within the preceding 6 months, were required to use a generic antidepressant. The member copayment was waived for the first prescription. All generic antidepressants were in tier 1 of the drug formulary, with an average copayment of $5 to $10. All brand-name antidepressants were in either tier 2 (preferred brand), with an average copayment of $20 to $25 or 25% coinsurance, or tier 3 (nonformulary brand), with an average copayment of $40 to $45 or 50% coinsurance. Pharmacy claims data from a national pharmacy benefit manager (PBM) without interventions for antidepressants in 2004 or 2005 were used for the comparison group. RESULTS: The generic antidepressant dispensing rate increased by 20 points (32.5% to 52.5%) in the intervention group but only 7.4 points (24.9% to 32.3%) in the comparison group in 2005 compared with 2004. The principal measure of antidepressant drug cost per day of therapy in the intervention group decreased by 11.7% (from $2.40 to $2.12) in 2005 compared with 2004 versus a 2.7% decrease (from $2.60 to $2.53) in the comparison group (P <0.001). Days of antidepressant drug therapy per member per month (PMPM) dropped by 1.5% (from 1.74 to 1.71) in the intervention group versus a decrease of 5.0% (from 1.37 to 1.30) in the comparison group in 2005 compared with 2004. The combination of change in drug cost and utilization resulted in a 13.0% decrease in antidepressant drug cost, from $4.16 PMPM in 2004 to $3.62 in 2005, compared with a 7.6% decrease (from $3.57 to $3.30 PMPM) in the comparison group. The 9.0% difference in drug cost per day represents drug cost savings of approximately $0.36 PMPM or $1,880,562 in 2005 dollars for this HMO of approximately 440,000 members. CONCLUSION: A step-therapy edit requiring HMO members to use a generic antidepressant, excluding tricyclics, prior to use of a brand-name antidepressant resulted in drug cost savings of 9.0% for the entire class of antidepressants, equal to $1,880,562 ($0.36 PMPM) in 2005 dollars in the first year of the intervention. A small (-1.5%) decrease in use of antidepressants occurred in the intervention group, which was less than the 5.0% decrease in utilization of antidepressants in the comparison group.

Comparação do volume da gota e custo do tratamento dos genéricos de maleato de timolol 0, 5 por cento / Drop volume and cost of treatment with generic 0.5 percent timolol maleate preparations

OBJETIVO: Comparar o volume da gota das medicações genéricas de maleato de timolol a fim de determinar o custo real do tratamento em relação à medicação de referência. MÉTODOS: Foi determinado o volume da gota do Timoptol® 0,5 por cento (Merck Sharp & Dome) e dos genéricos maleato de timolol 0,5 por cento dos laboratórios Allergan-Lok, Cristália e Falcon. Cinco frascos de 5 ml de cada medicação foram adquiridos no mercado. Dez gotas de cada frasco foram pesadas em balança de precisão individualmente, bem como, um mililitro de cada frasco para a determinação do volume da gota. Com base no volume da gota foi calculada a duração média em dias e o custo anual, considerando-se o gasto diário de 4 gotas e o preço máximo ao consumidor publicado em maio de 2003 com alíquota de 18 por cento. RESULTADOS: Observaram-se diferenças estatisticamente significantes do volume da gota entre as medicações (p<0,0001 por cento). A maior gota foi a do maleato de timolol 0,5 por cento Allergan-Lok (35,1 æl) e a menor do maleato de timolol Falcon (27,3 æl). A medicação de referência (Timoptol®) proporcionou gota média de 27,9 æl. O custo anual do tratamento foi de R$ 68,87 para o Timoptol, de R$ 72,76 para o maleato de timolol Allergan-Lok, de R$ 50,00 para o maleato de timolol Cristália e de R$ 43,11 para o maleato de timolol Falcon (p<0,0001). O maleato de timolol Allergan-Lok foi estatisticamente mais caro que os demais sendo 68,8 por cento mais oneroso que o mais barato. CONCLUSAO: Existem diferenças no volume da gota das medicações genéricas acarretando diferenças no custo anual do tratamento. O volume da gota deve ser considerado na análise de qualidade dos medicamentos antiglaucomatosos genéricos.

Medications taken by 26-year-olds.

BACKGROUND: Most descriptive pharmacoepidemiological reports are from studies of older people, and little is known about medication use by younger adults. AIMS: The aim of the present study was to examine the prevalence of medication usage in the previous 2 weeks among young adults. METHODS: Detailed information was collected on medications taken by 26-year-old participants in the longstanding Dunedin Multidisciplinary Health and Development Study. RESULTS: At age 26, 980 (96.2%) of the surviving cohort participated; medication data were available for 978 individuals, of whom 78.1% had taken one or more prescribed or over-the-counter medications. Medication use was higher among females. The most prevalent drug categories were analgesics (taken by 22.8% of the sample), hormonal contraceptives (21.9%; 44.7% of females), nutrient supplements (17.6%) and anti-asthma drugs (11.1%). CONCLUSIONS: The prevalence and pattern of medication use among younger adults differ from those reported for older age groups. Asthma appears to be the most prevalent chronic medical condition requiring pharmacological intervention (and for which medical care has been sought) among younger adults. The low rates of use of antidepressants and anxiolytics suggest that common psychiatric disorders may currently go unrecognized or untreated among young adults, and the high prevalence of 'third generation' oral contraceptive use among females is of particular concern.