Food Increases the Bioavailability of Isotretinoin

Abstract

Twenty healthy male subjects received 80 mg (2 X 40 mg SEG capsules) oral isotretinoin separated by two-week washout periods in an open randomized crossover design. Isotretinoin was administered during a complete fast, 1 hour after a standard breakfast, with a standard breakfast, or 1 hour before a standard breakfast. Blood samples were obtained at specific times over a 72-hour period. Isotretinoin blood concentrations were determined by a specific HPLC method. The relative bioavailability (AUC) of isotretinoin was found to be approximately 1.5 to 2 times greater when the dose was administered 1 hour before, concomitantly with, or 1 hour after a meal than when it was given during a complete fast. In addition, because the Cmax value is lower when the dose is administered with food rather than 1 hour after a meal, coadministration of isotretinoin with food may be the best method of administration.

Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in children with high-risk neuroblastoma – a study of the United Kingdom Children's Cancer Study Group

“…No attempt was made to control food intake around the time of administration. A previous study has reported higher plasma concentrations when 13-cisRA was administered within 1 h before or after a standard meal, compared with the fasted state (Colburn et al, 1983). Application of the data presented here to guide dosing of 13-cisRA would also need to be adapted to reflect differences in the administration of 13-cisRA in different countries, for example punching a hole in the capsule so that it can be chewed before swallowing.…”

Status Report on Oral Isotretinoin in the Management of Acne Vulgaris: Why All the Discussion about Drug Absorption and Relapse Rates?

“…The subset of patients who needed at least one additional course of OI usually completed this within 2 to 3 years, of their initial course [1, 4, 12••, 13-17••, [18][19][20][21][22][23][24][25]. Given the same duration of OI therapy which was usually 16 to 20 weeks, a consistent trend for recurrence of AV has been observed in several studies, with a lower daily dose (0.1 -0.2 mg/kg/day) associated with a higher recurrence rate and often an earlier onset of recurrent AV as compared to higher daily doses (0.5-mg/kg/day; 1 mg/ kg/day) [12••, 13-17••, [18][19][20][21][22][23][24][25]. The culmination of data analysis supports that a course of OI achieves a total dose of 120 -50 mg/kg to reduce the potential for recurrence of AV (Table 1) [17••, 18-22].…”

Structure-activity relationships of retinoids in developmental toxicology

“…Human pharmacokinetic data could be described by bi-or triexponential equations (Khoo et al, 1982), but a recycling model fit the plasma data best. The presence of food in the gut and the type of pharmaceutical preparation (Colburn et al, 1983b;Shelley et al, 1982) can affect the absorption of the drug. Peak circulating plasma concentrations and bioavailablility were greater when the drug was administered following a meal than when the gut was empty (Colburn et al, 1983b).…”

“…The presence of food in the gut and the type of pharmaceutical preparation (Colburn et al, 1983b;Shelley et al, 1982) can affect the absorption of the drug. Peak circulating plasma concentrations and bioavailablility were greater when the drug was administered following a meal than when the gut was empty (Colburn et al, 1983b). The elimination half-lives in man ranges from 4 (Kerr et al, 1982) to 13 to 14 (Colburn et al, 1983a) to 25 h (Goodman et al, 1982; Neither the parent nor its metabolite, all-.tmru.-RA, is eliminated in the urine; they are primarily eliminated in the feces (Khoo et al, 1982).…”