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Background: Busulfan pharmacokinetics exhibit large inter-subject variability. Our objective was to evaluate the influence of glutathione S-transferase A1 (GSTA1) gene variants on busulfan oral clearance (CLo) in a population of patients undergoing hematopoietic stem cell transplantation. Methods: This is a quasi-experimental retrospective study in adult patients (n = 87 included in the final analyses) receiving oral busulfan. Pharmacokinetics data (area under the plasma concentration-time curve (AUC) determined from 10 blood samples) were retrieved from patients’ files and GSTA1 *A and *B allele polymorphisms determined from banked DNA samples. Three different limited sampling methods (LSM) using four blood samples were also compared. Results: Carriers of GSTA1*B exhibited lower busulfan CLo than patients with an *A/*A genotype (p < 0.002): Busulfan CLo was 166 ± 31, 187 ± 37 vs. 207 ± 47 mL/min for GSTA1*B/*B, *A/*B and *A/*A genotypes, respectively. Similar results were obtained with the tested LSMs. Using the standard AUC method, distribution of patients above the therapeutic range after the first dose was 29% for GSTA1*A/*A, 50% for *A/*B, and 65% for *B/*B. The LSMs correctly identified ≥91% of patients with an AUC above the therapeutic range. The misclassified patients had a mean difference less than 5% in their AUCs. Conclusion: Patients carrying GSTA1 loss of function *B allele were at increased risk of overdosing on their initial busulfan oral dose. Genetic polymorphisms associated with GSTA1 explain a significant part of busulfan CLo variability which could be captured by LSM strategies.

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Conflicting results have been reported on the value of the steatocrit as a screening test for steatorrhea. We recently modified the test procedure by fecal acidification with the hope of improving fat extraction and consequently the sensitivity of the test. The aim of the present study was to ascertain whether or not fecal acidification led to improved fat extraction by comparing the fat content of both fatty and solid layers obtained by centrifugation of 12 acidified (acid steatocrit) and unacidified (classical steatocrit) steatorrheal stool samples. The fat content of fatty and solid layers was evaluated using the semiquantitative (+ = 1, +2 = 2, +3 = 3) scoring system described by Drummey for the interpretation of the Sudan microscopic method for fecal fat. The fatty layers sum of scores for the 12 samples examined was 31 and 16 for the acid and classical steatocrit, respectively. The solid layers sum of scores for the 12 samples was 13 and 24 for the acid and classical steatocrit, respectively. Fat extraction from stool samples was significantly improved after fecal sample acidification (p < 0.005). Acid steatocrit results agreed better with chemically measured fecal fat than classical steatocrit results. We conclude that fecal acidification, by improving fat extraction, increases the reliability of the steatocrit method for the detection of steatorrhea.