Bioequivalence and Bioavailability Forum

Passing SD and Failing MD [General Sta­tis­tics]

posted by luvblooms  – India, 2013-11-29 19:57 (4173 d 10:19 ago) – Posting: # 11991
Views: 14,501

Hi HS,

❝ That’s an interesting story! Were the PEs in the MD study shifted to the same direction (i.e., were in MD the ratios also <100%)? How did the CVs “behave”?

Yes, the ratio's were on lower side.The T/R ratio was ~87 for Cmin (lower CI was 76.8) and Same was the case for AUCtss (~89 with range of 78-99).

CVs were almost similar to that of SD.

When we were trying to understand the reason of failure, one thing that draw our attention was the lower AUC values in SD. And this lower accumulations might have lead to the lower Cmin and AUCtss.

Further modified the formula in order to achieve AUC (by increasing its solubility in lower GIT) and dosed it for SD and BINGO!!! Cmax ~96% AUC= 95 (still was not able to reach 100). When the same was dosed for MD, it passed with flying colors (Cmin and AUCtss ratios were 93 and 94 respectively)

❝ The only case I know from the literature is quite old.*

❝

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• Van Hoogdalem EJ, Terpstra IJ, Krauwinkel WJJ, Volkers-Kamermans NJ, Baven, ALM, Verschoor JSC. Multiple dose bioequivalence study with josamycin propionate, a drug with highly variable kinetics, in healthy volunteers. Int J Clin Pharmacol Ther. 1996;34(5):202–7.

Read this article long back, need to refresh the memory

Regards

Complete thread:

• Simulation of data to predict Steady state cakhatri 2013-11-24 10:13 [General Sta­tis­tics] 
  • Nonparametric superposition Helmut 2013-11-24 14:30
    • Nonparametric superposition jag009 2013-11-24 23:13
      • Nonlinear nightmare Helmut 2013-11-25 02:56
        • Nonlinear nightmare jag009 2013-11-25 17:43
          • Nonlinear nightmare Helmut 2013-11-26 14:32
            • Nonlinear nightmare jag009 2013-11-26 16:00
              • OT: Vienna Helmut 2013-11-26 16:27
                • OT: Vienna jag009 2013-11-26 17:29
                  • OT: Vienna Helmut 2013-11-27 13:04
    • Conc at dosing interval jag009 2013-11-25 17:48
      • Conc at dosing interval Helmut 2013-11-26 15:01
        • Conc at dosing interval jag009 2013-11-26 17:31
          • Conc at dosing interval Helmut 2013-11-27 13:10
            • Conc at dosing interval jag009 2013-11-27 20:00
            • Passing SD and Failing MD luvblooms 2013-11-28 09:19
              • Passing SD and Failing MD Helmut 2013-11-29 17:29
                • Passing SD and Failing MDluvblooms 2013-11-29 18:57
                  • Cτ predictive of Cmin Helmut 2013-11-30 17:25