Relationship between amikacin pharmacokinetics and biological parameters associated with organ dysfunction: a case series study of critically ill patients with intra-abdominal sepsis.

OBJECTIVES: This study aimed to evaluate the relationship between amikacin pharmacokinetics and the biomarkers associated with organ dysfunction in critically ill patients with intra-abdominal sepsis. METHODS: A case series involving critically ill patients with intra-abdominal sepsis who received an amikacin loading dose of 20-25 mg/kg intravenous infusion was studied. The 1-, 2-, 4-, 6- and 24-hour amikacin serum concentrations were measured to calculate the pharmacokinetic parameters. The Sequential Organ Failure Assessment (SOFA) score, white blood cells, neutrophil to lymphocyte ratio, platelet count, serum creatinine, creatinine clearance, bilirubin, partial pressure of oxygen to fraction of inspired oxygen ratio, serum albumin, procalcitonin, lactate level, erythrocyte sedimentation rate (ESR) and C-reactive protein were recorded. A linear regression analysis was performed to examine the relationship between the amikacin pharmacokinetics and the biological parameters. RESULTS: Twenty-one patients were studied. A significant correlation was found between the volume of distribution and ESR (p<0.05, r=0.844). Moreover, drug clearance had a significant inverse correlation with serum lactate (p<0.05, r=-0.603). No other significant correlations were found. CONCLUSIONS: ESR and serum lactate were identified as useful predictors of amikacin pharmacokinetics in critically ill patients with intra-abdominal sepsis and may help guide the selection of appropriate empirical dosing.

Imatinib Efficacy, Safety and Resistance in Iranian Patients with Chronic Myeloid Leukemia: A Review of Literature.

Background: Imatinib is the gold standard in the treatment of chronic myeloid leukemia (CML) patients. Resistance to imatinib is interfering with patients' responses and their survivals. Materials and Methods: We designed a systematic search to find relevant studies by applying appropriate keywords in PubMed, Web of science, Scopus, Ovid, ProQuest, Science direct and Google scholar for English studies. We also investigated the aforementioned terms' correspondence in Magiran, Scientific information database (SID) and Google scholar for Persian articles. Results: 25 studies were selected for final analysis. Reported hematologic responses from adult studies ranged 86-99% and major molecular responses were estimated in 38.84% of our patients within 12 months of treatment. The most frequent reported adverse drug reactions (ADRs) were edema (n=5 studies, 100%) and fatigue and nausea (n=4 studies, 80%); ADR per capita ratio was 1.46. Only one study informed ADRs in pediatrics demonstrating 93% of patients experienced ADRs after receiving imatinib. Most of the Studies (n=4, 67% from 7 studies) considered BCR/ABL point mutation as main reason of imatinib resistance. Drug-binding site and P-loop regions were two common sites for BCR/ABL point mutation. Conclusion: Imatinib as the first line treatment for CML has been associated with proper and durable responses in Iranian adults and children CML patients. Moreover, Imatinib life-threatening adverse effects were reported uncommon. Various responses to modified regimens have been reported in resistant patients; therefore, individualized treatment based on mutation type could be recommended.

Evaluation of Amikacin Pharmacokinetics in Critically Ill Patients with Intra-abdominal Sepsis.

Purpose: Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis. Methods: Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient. Results: There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, P=0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, P=0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (P=0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, P=0.015). Conclusion: Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.