Kinetics of absorption of a new once-a-day formulation of theophylline in the presence and absence of food.
Two three-way crossover studies were done to characterize the drug release characteristics of Monospan (3M Pharmaceuticals, St. Paul, MN) capsules, a new once-a-day theophylline formulation. In the first study, 22 healthy males received single 450-mg doses of Monospan in the presence and absence of a high-fat breakfast; the same dose of Somophyllin (Fisons, Rochester, NY) immediate-release liquid was given to fasted subjects as a reference. The second study involved 29 healthy males given a single dose of 900 mg of Monospan in the presence and absence of the same high-fat meal; Theo-24 (G. D. Searle and Co., Skokie, IL) capsules were given to fasted subjects as a reference. The results of both studies showed that food did not affect the absorption of theophylline from Monospan; peak concentration, to and area under the serum concentration-time curve were all unchanged. The absorption rates were similar with both strengths and dietary conditions and showed that theophylline was absorbed slowly from Monospan at a constant rate (approximately 3.2%/h) over 24 h. Absorption continued past 24 h, and the extent of absorption from Monospan compared with that from each reference averaged 88% or higher. A good correlation (r > 0.980) was observed for Monospan between the amount absorbed in vivo and the amount released in the in vitro dissolution test, a result that demonstrates the precise rate control of Monospan. We conclude that Monospan is a suitable once-a-day formulation that can be taken without regard to food.
Harrison
L I
LI
3M Pharmaceuticals Division, St. Paul, MN 55144.
Mitra
A K
AK
Kehe
C R
CR
Klinger
N M
NM
Wick
K A
KA
McCarville
S E
SE
Cooper
K M
KM
Chang
S F
SF
Roddy
P J
PJ
Berge
S M
SM
D000042:Absorption; D000293:Adolescent; D000328:Adult; D000628:Aminophylline / Q000493:pharmacokinetics; D002214:Capsules; D003692:Delayed-Action Preparations; D004041:Dietary Fats / Q000008:administration & dosage; D004304:Dosage Forms; D005502:Food; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D013806:Theophylline / Q000493:pharmacokinetics*
D002214:Capsules; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D004304:Dosage Forms; D000628:Aminophylline; D013806:Theophylline