Bioequivalence and Bioavailability Forum

Hi Imph,

❝ For the estimation of the terminal rate constant (lambda_z) using the two time tmax method, how do we choose the best number of points once the mono exponential phase has been identified?.

Not sure whether I understand you question… With TTT you get the starting point, then use all others until t_last. However, the TTT method (like any other algorithm) works best for IR formulations but might fail on ‘flat’ profiles (controlled re­lease formulations with flip-flop PK) or on profiles of multiphasic release formulations.
Hence, visual inspection of fits is mandatory.^1–4

---

1. Schulz H-U, Steinijans VW. Striving for standards in bioequivalence assessment: a review. Int J Clin Pharm Ther Toxicol. 1991; 29(8): 293–8. PMID 1743802.
   
2. Sauter R, Steinijans VW, Diletti E, Böhm E, Schulz H-U. Presentation of results from bioequivalence studies. Int J Clin Pharm Ther Toxicol. 1992; 30(7): 233–56. PMID 1506127
   
3. Hauschke D, Steinjans V, Pigeot I. Bioequivalence Studies in Drug Development. Chichester: Wiley; 2007. p. 131.
   
4. Scheerans C, Derendorf H, Kloft C. Proposal for a Standardised Identification of the Mono-Exponential Ter­mi­nal Phase for Orally Administered Drugs. Biopharm Drug Dispos. 2008; 29(3): 145–57. doi:10.1002/bdd.596.