1.Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice.
Moo, Kai Shing ; Radhakrishnan, Shantini ; Teoh, Magdalene ; Narayanan, Prasad ; Bukhari, Nadeem Irfan ; Segarra, Ignacio
Acta Pharmaceutica Sinica 2010;45(7):901-8
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.
2.Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice.
Kai Shing MOO ; Shantini RADHAKRISHNAN ; Magdalene TEOH ; Prasad NARAYANAN ; Nadeem Irfan BUKHARI ; Ignacio SEGARRA
Acta Pharmaceutica Sinica 2010;45(7):901-908
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
3.Does the attire of a primary care physician affect patients’ perceptions and their levels of trust in the doctor?
Haymond Prasad Narayanan ; Zahrina Azian binti Zohadie ; Rosanna Patricia Chryshanthi Gregory ; Rosalind Ho Wan Ying ; Rajini Ann S. Ratnasingam ; Low Boon Teck ; Ping Yein Lee
Malaysian Family Physician 2018;13(3):3-11
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.