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Intraindividual variations of 8-methoxypsoralen plasma levels
Abstract:
Intraindividual variations of 8-methoxypsoralen (8-MOP) plasma levels were investigated. On at least 3 consecutive days of treatment 8-MOP levels were determined 2 h following the administration of 0.56-0.82 mg/kg b.w. On day 1 a complete plasma level-time profile was obtained. Interindividually, 8-MOP plasma levels varied from 0-654 ng/ml. Intraindividual variation was considerably less being 1.2-5.3-fold. In one patient who showed a lower absorption rate of 8-MOP plasma levels varied from 0-126 ng/ml. There was a rather close correlation (r = 0.81) of the variation of 8-MOP plasma levels (determined as the ratio of highest to lowest plasma level) and mean plasma level, intraindividual variation decreasing exponentially with increasing 8-MOP plasma levels. Parameters determining variation of 8-MOP plasma levels are the intrinsic hepatic clearance, liver blood flow, and possibly the absorption of the drug from gastrointestinal tract. To keep intraindividual variation as low as possible ingestion of the drug together with a standardized meal is suggested. Drugs interfering with hepatic metabolism or liver blood flow should be avoided.
Insights
This study investigated 8-methoxypsoralen (8-MOP) plasma levels, finding that intraindividual variations were significantly less than interindividual ones. Standardized meals can help minimize these variations for consistent drug absorption.
Area of Science:
- Pharmacokinetics
- Photochemotherapy
- Drug Metabolism
Background:
- 8-methoxypsoralen (8-MOP) is a crucial photosensitizing agent used in photochemotherapy.
- Understanding plasma level variations is essential for optimizing therapeutic efficacy and minimizing adverse effects.
Purpose of the Study:
- To investigate the extent of intraindividual variations in 8-methoxypsoralen (8-MOP) plasma levels.
- To identify factors contributing to these variations and suggest methods for minimizing them.
Main Methods:
- 8-MOP plasma levels were measured 2 hours post-administration over consecutive treatment days (0.56-0.82 mg/kg b.w.).
- Plasma level-time profiles were generated on day 1.
- Inter- and intraindividual variations were quantified.
Main Results:
- Significant interindividual variations in 8-MOP plasma levels (0-654 ng/ml) were observed.
- Intraindividual variations were considerably lower, ranging from 1.2- to 5.3-fold.
- A close correlation (r=0.81) was found between plasma level variation and mean plasma level, with variation decreasing exponentially as mean levels increased.
- Factors influencing variation include hepatic clearance, liver blood flow, and gastrointestinal absorption.
Conclusions:
- Intraindividual variation in 8-MOP plasma levels is less pronounced than interindividual differences.
- Standardized meal intake with 8-MOP can help minimize plasma level fluctuations.
- Avoiding co-administered drugs that affect hepatic metabolism or liver blood flow is recommended.