Clinical pharmacokinetics of tacrolimus in iranian liver transplant recipients

Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients' medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program [Monolix version 3.1]. Absorption rate constant was fixed at two hours[-1]. Drug apparent clearance [CL/F], apparent volume of distribution [Vd/F], and elimination half life [t1/2 Beta] were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t1/2 Beta were found to be 9.3 +/- 0.96 L/h, 101 +/- 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t«? of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations

Elevated vancomycin trough concentration: increased efficacy and/or toxicity?

Vancomycin susceptibility of methicillin-resistant Staphylococcus aureus has been changed over time and its average minimum inhibitory concentration increased from 1.5 to 1.75 mg/L.A recently published guideline by the American Society of Health Pharmacist recommended a daily dose of 15-20 mg/Kg every 8 to 12 hours of vancomycin to achieve a trough concentration between 15-20 mg/L for treatment of severe infections. Medical records of 69 patients from infectious ward of Imam Khomeini hospital, with suspected or confirmed gram-positive infection who had at least one trough level of vancomycin, were evaluated regarding vancomycin therapeutic goal; efficacy and renal safety. Most of patients [60.6%] with severe infections did not achieve the recommended vancomycin trough level during treatment course. Time to normalization of the signs and symptoms of infection did not correlate with the patients' serum vancomycin trough levels. At the end of treatment course, there was no significant correlation between patients' creatinine clearance and vancomycin trough levels [P=0.32]. However, patients'cratinine clearance showed a negatively significant correlation with trough level of vancomycin [P=0.01]. Vancomycin induced nephrotoxicity was detected in 4.3% of the patients. These data showed that vancomycin trough level may not necessarily assure treatment success, and also it would not essentially predict the risk of vancomycin induced nephrotoxicity. However, more well designed studies with larger sample size needed for better clinical and practical judgment

Impact of UGT1A9 polymorphism on mycophenolic acid pharmacokinetic parameters in stable renal transplant patients

There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil [MMF] among transplanted patients. Some studies have shown that single nucleotide polymorphisms [SNPs] of the Uridine Diphosphate Glucuronosyl Transferase1A9 [UGT1A9] are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran. Blood samples were taken from 40 de novo stable Iranian renal transplant patients taking 2 g MMF daily with Sr[Cr]

The role of clinical pharmacy services in achieving treatment targets in Iranian haemodialysis patients

<p><b>INTRODUCTION</b>The number of patients suffering from chronic kidney disease (CKD) is increasing worldwide. Hyperphosphataemia and high serum calcium (Ca) and phosphorus (P) product contribute to the substantial increase in cardiovascular events in CKD patients. Although reports of CKD complications in Iranian haemodialysis (HD) patients are comparable to data from other developed countries, management of these complications has failed to meet generally accepted targets. This study evaluated the impact of clinical pharmacy services in the management of complications in HD patients.</p><p><b>METHODS</b>During a six-month prospective study, clinical pharmacists conducted medical visits in the HD ward and adjusted the patients' medications according to their laboratory findings.</p><p><b>RESULTS</b>Serum Ca concentration was increased in hypocalcaemia patients and decreased in hypercalcaemia patients until it reached the optimal range in both groups. A decline in serum P level was noted in hyperphosphataemia patients, although it did not reach the target range. The Ca × P product decreased in patients with Ca × P > 55 mg2/dL2. Although it did not reach the goal, there was an increase and decrease in serum intact parathyroid hormone (iPTH) concentration in suboptimal and supraoptimal range patients, respectively. Serum Ca, P and iPTH levels did not change in patients with optimal values at the initiation of the study. Haemoglobin concentration increased in anaemic patients and serum ferritin reached target values in all patients. Total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased to near-optimal values in dyslipidaemia patients.</p><p><b>CONCLUSION</b>This study showed that clinical pharmacy services at the HD centre can improve the management of complications in CKD patients.</p>

Changes in 4-year antimicrobial resistance pattern of gram-positive bacteria at the main referral teaching hospital, Tehran, Iran

Infectious diseases are one of the most common causes of morbidity and mortality and the spread of resistant microorganisms is playing a significant role in this regard. The purpose of this study was to assess the trend in antimicrobial resistance of gram-positive bacteria at the main referral teaching hospital in Tehran during a 4-year period. All patients' biological isolates such as blood, urine, wound drainage, synovial fluid, sputum, and cerebrospinal fluid sent to the central laboratory of the hospital from 2007 to 2010 for identification and subsequently, antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method were considered. All isolates [100%] of S. aureus were sensitive to vancomycin and linezolid and resistant to amoxicillin. The rate of S. aureus resistance to oxacillin increased from 60.78% in 2007 to 72% in 2010. All isolates of Streptococci in 2007 and 2008 were sensitive to vancomycin; while, 3.33% and 4.76% of Streptococci isolates were reported to be vancomycin-resistant in 2009 and 2010, respectively. Enterococci isolated from the entire specimens were identified to be sensitive to teicoplanin and linezolid and resistant to cloxacillin and oxacillin. The rates of Enterococci sensitivity to vancomycin were 90.91%, 81.25%, 86.67%, and 93.3% in 2007, 2008, 2009, and 2010, respectively. Changes of antibiotics sensitivity against g positive pathogens were significant during four years in this study. To minimize the spread of resistant gram positive pathogens, periodic and regular surveillance of antimicrobial resistance pattern is highly recommended.

Adherence to empiric antibiotic therapy guideline in a referral teaching hospital, Tehran, Iran

Antibiotic guidelines have proven to be a simple and effective intervention to guide the choice of appropriate empiric antibiotic regimens. The goals of this study were to evaluate adherence to guidelines and streamlining of antibiotics. Hospital records of hospitalized patients in infectious diseases ward Imam Khomeini Hospital, Tehran, Iran, from May 2008 to September 2009 were reviewed. Adherence to guideline was defined as the use of empiric antibiotic in accordance with the clinical diagnosis and local guideline recommendations. In this study, 528 patients with a confirmed infectious disease diagnosis were considered for analysis. The four most frequent diagnoses were skin and soft tissue infections, tuberculosis, respiratory tract infections, and HIV associated opportunistic infections. The most frequent prescribed antibiotic was ceftriaxone. Overall adherence to guideline was 70.8% and the adherence for the most frequent diagnosis was 68%. Frequency of compatibility with the guidelines for were administrated regimes on the basis of drug selection, dosage form and drug dosing were 86.2%, 97% and 84.7%, respectively. The mean lag time between patients' hospital admission and starting empiric therapy was 1.69 +/- 4.9 days. In general, physicians' adherence with guidelines for empiric antibiotic therapy was high in infectious disease ward with a justified delay. Larger studies are required to establish these conclusions