ABSTRACT
In many manufacturing procedures, a large number of identical particles need to be disseminated uniformly into a given space. The uniformity of the spatial distribution of the particles can be critical to the properties of the final products. We proposed an image processing-based non-destructive technique to evaluate the particles' spatial uniformity in a spherical space imaged with computed tomography. Both graphic (qualitative) and numerical (quantitative) methods were developed to demonstrate the (non-) uniformity of the particles. Simulation results indicated that the technique helped detecting the non-uniformity in the particles' spatial distribution accurately. We conclude that the proposed technique can be used to test whether a number of particles in a sphere are uniformly distributed statistically and graphically.
ABSTRACT
OBJECTIVE: To investigate the association of CYP3A5 and MDR1 genetic polymorphisms with the concentration/ dose (C/D) ratio of tacrolimus for the feasibility of individualized medication. METHODS: The concentration of tacrolimus was detected by enzyme-multiplied immunoassay technique, and was adjusted by weight and dosage to C/D ratios. The single nucleotide polymorphisms of CYP3A5 A6986G and MDR1 C3435T, G2677T/ A, T1236C were determined by TaqMan RT-PCR. The differences of C/D ratio were compared among all of the genotype groups. RESULTS: There were 5 cases with CYP3A5 *1/*1, 22 cases with CYP3A5 *1/*3, and 33 cases with CYP3A5 *3/*3. The C/D ratios of the patients with at least one CYP3A5 *1 allele (130.40 +/- 53.94) was significantly lower than those with CYP3A5 *3/*3 (198.12 +/- 90.80) (P < 0.01). For MDR1, there were 22, 23 and 15 recipients carried C/C, C/T and T/T respectively in C3435T, and 8, 32 and 20 recipients carried T/T, T/ C and C/C respectively in T1236C. The carriers with G/G, G/T, G/A, T/A, T/T were 9, 24, 5, 8 and 14 respectively in G2677T/A. No significant difference was found in the C/D ratios of tacrolimus among different MDR1 genotypes. CONCLUSIONS: Determination of CYP3A5 genotype could help individualize tacrolimus dose regimen prospectively. The patients with CYP3A5 *3 *3 require less dose of tacrolimus to reach the same concentrations comparing with the patients with at least one CYP3A5 * 1 allele.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Cytochrome P-450 CYP3A/genetics , Kidney Transplantation , Liver Transplantation , Polymorphism, Single Nucleotide , Tacrolimus/blood , ATP Binding Cassette Transporter, Subfamily B , Adult , Aged , Female , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Male , Middle Aged , Tacrolimus/pharmacokinetics , Young AdultABSTRACT
OBJECTIVE: To identify rational dosage regimen for pazufloxacin methanesulphonate injection through a pharmacokinetics/pharmacodynamics (PK/PD) study. METHODS: Pazufloxacin methanesulphonate at the doses of 300 mg and 500 mg were injected to 24 healthy volunteers. The plasma concentrations of pazufloxacin were measured by RPHPLC-UV. The MICs of pazufloxacin against 130 strains of 7 species of bacterias, as well as the MPCs of pazufloxacin against 5 species of bacterias were measured by double broth dilution method. RESULTS: The AUC0-24/MIC50 of pazufloxacin methanesulphonate at a stabilized concentration state against methicillin-sensitive Staphylococcus aureus (MSSA) and S. pneumoniae were 215.36 and 107.68 at the dose of 300 mg, and 309.60 and 154.80 at the dose of 500 mg, respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 mg, and 81.28 and 40.64 at the dose of 500 mg, respectively. However, the AUC0-24/MIC of pazufloxacin methanesulphonate against methicillin-resistant staphylococcus aureus (MRSA) were far less than 40. Both the AUC0-24/MIC50 and the Cmax/MIC50 of pazufloxacin against P. aeruginosa at the doses of 300 mg and 500 mg exceeded the defined criteria 100 and 10. Whereas the AUC0-24/MIC and Cmax/MIC of pazufloxacin against E. coli, K. pneumoniae and A. baumanii were much less than 100 and 10. The capability of pazufloxacin methanesulphonate to prevent mutations of MSSA was strong at the dose of 500 mg, but not for other pathogenic bacteria either at 300 mg or 500 mg. CONCLUSION: Pazufloxacin methanesulphonate at the dose of 300 mg and 500 mg have similar efficacy in treating acute bacterial infections. The dosage regimen of 300 mg Q12h intravenous infusion is recommended.