Bioequivalence and Bioavailability Forum

Hi John!

❝ […] I saw from an article on "PK Modeling and Simulation of Mixed Pellets" by Watanalumlerd et at. The author listed a table:

❝ Parameter                Distribution        Mean+/-SD

❝ lag time of emptying     Log-Normal          0.75+/-0.22

❝ He wrote "A lognormal distribution was chosen ... because time cannot be negative"

The complete quote:^*

Gastric emptying time, lag time of emptying, and their variability (standard deviation) were obtained from the literature […]. A lognormal distribution was chosen for all time parameters because time cannot be negative.

I don’t have the referred literature but I have strong doubts that the sample sizes in these scintigraphy studies were large enough to distinguish between normal and lognormal distributions. I would suspect that reported arithmetic means ± SD were (erroneously) used by Watanalumlerd et al. BTW, they employed a nice software named Crystal Ball.

Time parameters in PK are a battleground. I wouldn’t opt for lognormal in simulations “because time cannot be negative” – unphysiological high values are still possible. I would rather go with a truncated normal (like in the paper of Csizmadia and Endrényi). The reasoning for truncated AUC₇₂ is also based on the fact that a GI transit time of larger than 72 hours was never observed in any study.

---

• Watanalumlerd P, Christensen JM, Ayres JW. Pharmacokinetic Modeling and Simulation of Gastrointestinal Transit Effects on Plasma Concentrations of Drugs from Mixed Immediate-Release and Enteric-Coated Pellet Formulations. Pharma Dev Technol. 2007;12:193–202. doi:10.1080/10837450701212750