The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipine.
The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I-III) participated in this ethically approved, randomised, cross-over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17-36 min. Plasma nifedipine levels were measured using a standard reverse-phase high-performance liquid chromatography method. The area under the plasma concentration-time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng x ml(-1) x h(-1)) was significantly higher than during the non-irradiation control session (median 174.5 ng x ml(-1) x h(-1)) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng x ml(-1) x h(-1)). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t 1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow.
Al-Ajmi
H S
HS
Photobiology Unit, University of Dundee, Clinical Pharmacology Group, University of Southampton, UK.
Dawe
R S
RS
Renwick
A G
AG
Macklin
B S
BS
Ferguson
J
J
Gibbs
N K
NK
D000328:Adult; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D017484:Dermatitis, Phototoxic / Q000097:blood / Q000209:etiology*; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics* / Q000528:radiation effects; D012016:Reference Values; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002121:Calcium Channel Blockers; D009543:Nifedipine