Z160 is dramatically more bioavailable when taken with a high fat meal.
Better hope our clinical trial participants are taking Z160 with a high fat meal!
A quote directly from the patent:
"Naturally, a high fat meal may not be recommended for many individuals being treated with compounds of formula 1, particularly those being treated for chronic conditions. However, for some individuals, particularly those being treated for acute conditions, administration of compounds of formula 1 with a high fat meal may be justified. In any event, bioavailability of compounds of formula 1 is significantly increased when administered with food, including either a normal fat meal or a high fat meal."
"SUMMARY OF THE INVENTION
A subject of the invention is the unexpected finding that administration of compounds of formula 1 with food markedly increases their extent of absorption when administered orally in human subjects. In particular, an aspect of the invention is a method of increasing the oral bioavailability of such compounds to a patient receiving treatment to modulate N-type calcium channels comprising administering to the patient a compound of formula 1 or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition, with food."
Snutch, Terrance P. (Vancouver, CA)
Fisher, Dennis M. (San Francisco, CA, US)
The new Z160 formulation increases bioavailability and reduces food effect, but the detailed trial protocol likely suggest that patients take Z160 with a meal. Preferably containing some fat. Should not be a problem in the U.S. and some fats recommended might be:
3. Olive Oil
5. Nut Butter
6. Fatty Fish
"By “fed” or “fed states” is meant a subject has eaten within about 30 minutes prior to drug administration. The meal can be a fatty meal, and the resulting mean pharmacokinetic parameters can be characteristic of consuming a fatty meal. For example, the “fed state” can be a human who has eaten a United States Food and Drug Administration (FDA) standard high fat breakfast (or another meal containing a comparable quantity of fat and calories) within 30 minutes prior to drug administration. A typical FDA standard breakfast consists of 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter, 4 ounces of hash brown potatoes, and 8 ounces of whole milk. The meal is high in both fat (approximately 50% of total calorie content of the meal) and calories (approximately 800-1,000 calories)."
SOLID DISPERSION FORMULATIONS AND METHODS OF USE THEREOF
"BACKGROUND OF THE INVENTION
The present invention relates to formulations and methods for increasing the bioavailability of 1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one or a metabolite thereof, as well as salts thereof. In particular, the formulations and methods relate to the use of solid dispersions to improve mean bioavailability in fasted or fed subjects and/or TO REDUCE food effect."