Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.

Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Benzamides ; Brain ; metabolism ; Drug Carriers ; administration & dosage ; chemistry ; Half-Life ; Imatinib Mesylate ; Injections, Intravenous ; Liposomes ; administration & dosage ; chemistry ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Inbred ICR ; Piperazines ; administration & dosage ; blood ; pharmacokinetics ; Pyrimidines ; administration & dosage ; blood ; pharmacokinetics ; Tissue Distribution

Introduction: With increasing evidence of disease transmission through doctors’ white coats, many countries have discouraged doctors from wearing their white coats during consultations. However, there have been limited studies about patients’ preferences concerning doctors’ attire in Malaysia. This study, therefore, aimed to investigate patients’ perceptions of doctors’ attire before and after the disclosure of information about the infection risk associated with white coats. Method: This cross-sectional study was conducted from 1st June 2015 to 31st July 2015 at three different primary care settings (government, private, and university primary care clinics) using a self-administered questionnaire. A 1:5 systematic random sampling method was employed to select the participants. The respondents were shown photographs of male and female doctors in four different types of attire and asked to rate their level of confidence and trust in and ease with doctors in each type of attire. Subsequently, the respondents were informed of the risk of white coat-carried infections, and their responses were reevaluated. Data analysis was completed using SPSS Version 24.0. Associations of categorical data were assessed using the Chi-Square test, while the overall change in perceptions after the disclosure of additional information was examined using the McNemar test. Results with p-values < 0.05 were considered statistically significant. Results: A total of 299 respondents completed the questionnaire. Most of the respondents had more confidence and trust in the male (62.5%) and female (59.2%) doctors wearing white coats. A high proportion of the respondents from the government clinic (70.5%) felt more confidence in male doctors dressed in white coats (p-value = 0.018). In terms of ethnicity, male doctors in white coats were highly favored by Malays (61.0%), followed by the Chinese (41.2%) and Indians (38%) (p = 0.005). A similar preference was observed for the female doctors, whereby the highest number of Malays (60.3%), followed by the Chinese (41.2%) and Indians (40.0%) (p = 0.006), had a preference for female doctors wearing white coats. Only 21.9% of the initial 71.9% of patients who preferred white coats maintained their preference (p < 0.001) after learning of the risk of microbial contamination associated with white coats. Conclusion: Most patients preferred that primary care doctors wear white coats. Nevertheless, that perception changed after they were informed about the infection risk associated with white coats.