Comparison of Branded and Generic Imatinib Plasma Concentrations in Patients With Chronic Myelogenous Leukemia: Unicentric Study.

INTRODUCTION: For over a decade, imatinib has been the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Doubts on the bioequivalence and bioavailability of emerging generic compounds have been expressed. Adequate imatinib plasma concentration ([IPC] ≥1000 µmol/L) is associated with a better chance of optimal treatment response in patients with CML. In this study, we compared the achieved IPCs between the branded compound and its 2 generic forms. PATIENTS AND METHODS: IPCs were compared in 24 consecutive patients with CML in the first chronic phase who changed from branded to generic imatinib. The median age was 49 years (range, 22-76 years). Fifteen of them were male. Six patients were switched to Neopax, 13 to Imakrebin, and 5 patients received both generics consecutively. All compounds were used in an equivalent dose of 400 mg orally once daily for at least 1 month before plasma concentrations were measured. High-performance liquid chromatography was used to determine imatinib plasma concentration from a specimen collected 21 to 24 hours after the last dose. RESULTS: The median IPC achieved with branded imatinib was 1454 µmol/L (range, 485-2707 µmol/L) with 18 patients (75%) having IPC ≥ 1000 µmol/L. For Neopax and Imakrebin, median IPCs were 1717 µmol/L (range, 1249-3630 µmol/L) and 1458 µmol/L (range, 707-880 µmol/L), respectively, with 11 of 11 (100%) and 16 of 18 (89%) patients having IPC ≥ 1000 µmol/L. No significant difference in measured IPCs between all 3 compounds was found (P > .257). CONCLUSION: When taken at equivalent doses, imatinib generics are bioequivalent and comparable in clinical efficacy and have the potential for substantial savings in the treatment cost for CML.

Ethylene glycol poisoning.

A 40-year-old man was admitted to the emergency department after a suicide attempt. The patient was found at home unconscious, with an open bottle of antifreeze near him. The patient was in a coma on admission, but neurological examination excluded intracranial changes. Results of initial urine and serum toxicological screening tests were negative. Laboratory values indicated metabolic acidosis, leukocytosis, urinalysis revealed hematuria and unrecognized crystals. Osmolality and osmol gap were not determined on patient admission. Treatment with ethanol as an antidote and hemodialysis were started because of metabolic acidosis, anamnestic data and clinical status of the patient, and subsequently led to improvement of his condition. Further toxicological analyses of glycolic and oxalic acids in serum and urine samples were performed by ion-chromatography (IC) method and showed high values in spot urine and serum ultrafiltrate at admission, but during therapy the values progressively decreased. Treatment of poisoned patient for 3 weeks resulted in complete recovery.