Population pharmacokinetics of tamsulosine in patients with benign prostatic hyperplasia.

PURPOSE: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. METHODS: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. RESULTS: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. CONCLUSION: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.

Contemporary surgical management of drug-resistant focal epilepsy.

Introduction: Seizures, which could not be controlled by drug therapy, have profound negative influence on the quality of life of the affected person. If with clear locus of origin and accompanied by loss of consciousness, drug-resistant epilepsy could be treated by surgery.Areas covered: The aim of this article was to review current status of epilepsy surgery through description of the most important operative methods and narrative comparison of their benefits and harms. In total 1154 articles were retrieved from MEDLINE, SCOPUS, EBSCO, and SCINDEKS databases, and 78 included in the review. The review included systematic reviews, meta-analyses, clinical trials, observational studies on humans, case series, and case reports.Expert opinion: Sophisticated diagnostic methods nowadays offer much more precise localization of epileptogenic focus and detailed planning of a surgical procedure which will make minimal damage of neural pathways and structures essential for movements, speech, cognition, and emotions. Advent of perioperative care, and improved diagnostics and surgical techniques resulted with significant drop in rates of postoperative complications, long-term neurological deficit, and mortality in the last decade, while seizure freedom rate and quality of life increased.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Population pharmacokinetics of carvedilol in patients with congestive heart failure.

The aim of this study was to derive population pharmacokinetic (PK) model for clearance (CL) of carvedilol in adult patients with chronic heart failure (CHF). Medication and demographic data were obtained from 52 Caucasian patients with CHF taking carvedilol. Population PK analysis was performed by nonlinear mixed-effects modeling (NONMEM) to estimate and identify different factors that could affect carvedilol CL. A total of 55 plasma concentrations were collected from 52 patients with mean age of 63.02 ± 11.95 years and total body weight (TBW) of 77.96 ± 13.46 kg. Total daily doses of carvedilol in the target population had wide range of variability (6.25-50 mg), followed by high variability of drug plasma concentrations (1-59.07 ng/mL). The typical mean value for carvedilol CL, estimated by the base model, in the target population was 43.8 L/h. The TBW, concomitant therapy with digoxin, and tobacco using were determinants of a derived population model. The final regression model for the CL of carvedilol is: [Formula: see text] Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability.