Population pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control.

AIMS: Gabapentin (GBP) is widely used to treat neuropathic pain, including diabetic neuropathic pain. Our objective was to evaluate the role of diabetes and glycaemic control on GBP population pharmacokinetics. METHODS: A clinical trial was conducted in patients with neuropathic pain (n = 29) due to type 2 diabetes (n = 19) or lumbar/cervical disc herniation (n = 10). All participants were treated with a single oral dose GBP. Blood was sampled up to 24 hours after GBP administration. Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm. Weight, body mass index, sex, biomarkers of renal function and diabetes, and genotypes for the main genetic polymorphisms of SLC22A2 (rs316019) and SLC22A4 (rs1050152), the genes encoding the transporters for organic cations OCT2 and OCTN1, were tested as potential covariates. RESULTS: GBP drug disposition was described by a 1-compartment model with lag-time, first-order absorption and linear elimination. The total clearance was dependent on estimated glomerular filtration rate. Population estimates (between-subject variability in percentage) for lag time, first-order absorption rate, apparent volume of distribution and total clearance were 0.316 h (10.6%), 1.12 h-1 (10.7%), 140 L (7.7%) and 14.7 L/h (6.97%), respectively. No significant association was observed with hyperglycaemia, glycated haemoglobin, diabetes diagnosis, age, sex, weight, body mass index, SLC22A2 or SLC22A4 genotypes. CONCLUSION: This population pharmacokinetics model accurately estimated GBP concentrations in patients with neuropathic pain, using estimated glomerular filtrationrate as a covariate for total clearance. The distribution and excretion processes of GBP were not affected by hyperglycaemia or diabetes.

Elucidating factors associated with non-adherence among Type 1 diabetes patients in primary care setting in Southeastern Brazil.

AIMS: To explore the factors associated with adherence and non-adherence to the pharmacological treatment of patients with T1DM in primary care setting southeast Brazil. METHODS: We conducted a cross-sectional study with 158 patients attending in the primary health care in the city of Franca southeast Brazil and measure adherence to antidiabetic medication. Adherence was measure using Morisky-Green Test modified. RESULTS: The majority of patients was adherence to antidiabetic medication (63.2%). More than one third of patients were non-adherent treated pharmacologically and comorbidities most prevalent were hypertension (63.8%), dyslipidemia (43.1%) and depression (32.8%). Depression were strongest predictor OR=2.8 (1.2-6.5) of non-adherence. CONCLUSION: Depression is a factor associated with non-adherence to pharmacological treatment in patients with T1DM, and in clinical practice, screening for depression and intervention as well as pharmaceutical care may improve adherence to pharmacotherapy.

Baseline characteristics and risk factors for ulcer, amputation and severe neuropathy in diabetic foot at risk: the BRAZUPA study.

BACKGROUND: Studies on diabetic foot and its complications involving a significant and representative sample of patients in South American countries are scarce. The main objective of this study was to acquire clinical and epidemiological data on a large cohort of diabetic patients from 19 centers from Brazil and focus on factors that could be associated with the risk of ulcer and amputation. METHODS: This study presents cross sectional, baseline results of the BRAZUPA Study. A total of 1455 patients were included. Parameters recorded included age, gender, ethnicity, diabetes and comorbidity-related records, previous ulcer or amputation, clinical symptomatic score, foot classification and microvascular complications. RESULTS: Patients with ulcer had longer disease duration (17.2 ± 9.9 vs. 13.2 ± 9.4 years; p < 0.001), and poorer glycemic control (HbA1c 9.23 ± 2.03 vs. 8.35 ± 1.99; p < 0.001). Independent risk factors for ulcer were male gender (OR 1.71; 95 % CI 1.2-3.7), smoking (OR 1.78; 95 % CI 1.09-2.89), neuroischemic foot (OR 20.34; 95 % CI 9.31-44.38), region of origin (higher risk for those from developed regions, OR 2.39; 95 % CI 1.47-3.87), presence of retinopathy (OR 1.68; 95 % CI 1.08-2.62) and absence of vibratory sensation (OR 7.95; 95 % CI 4.65-13.59). Risk factors for amputation were male gender (OR 2.12; 95 % CI 1.2-3.73), type 2 diabetes (OR 3.33; 95 % CI 1.01-11.1), foot at risk classification (higher risk for ischemic foot, OR 19.63; 95 % CI 3.43-112.5), hypertension (lower risk, OR 0.3; 95 % CI 0.14-0.63), region of origin (South/Southeast, OR 2.2; 95 % CI 1.1-4.42), previous history of ulcer (OR 9.66; 95 % CI 4.67-19.98) and altered vibratory sensation (OR 3.46; 95 % CI 1.64-7.33). There was no association between either outcome and ethnicity. CONCLUSIONS: Ulcer and amputation rates were high. Age at presentation was low and patients with ulcer presented a higher prevalence of neuropathy compared to ischemic foot at risk. Ischemic disease was more associated with amputations. Ethnical differences were not of great importance in a miscegenated population.

Prevalence of adults with type 1 diabetes who meet the goals of care in daily clinical practice: a nationwide multicenter study in Brazil.

OBJECTIVE: To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines. RESEARCH DESIGN AND METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 ± 9.8 years with diabetes duration of 14.3 ± 8.8 years. RESULTS: Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively. CONCLUSIONS: The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health.