RESUMO
BACKGROUND: Gastrointestinal side effects are associated with the oral ingestion of 8-methoxsalen (8-MOP), including the liquid and crystalline formulations. OBJECTIVE: The objective of this study was to determine whether the gastrointestinal symptoms associated with 8-MOP could be decreased by altering the route of administration. METHODS: In an open pilot study, 8-MOP rectal suppositories were given to six patients with psoriasis vulgaris who had significant nausea or abdominal pain with the oral liquid form of the drug. RESULTS: On a scale of 0 to 5, this group of patients reported a mean score of 4.4 for nausea, 0.3 for vomiting, 2.1 for abdominal pain, and 1.3 for headaches with oral 8-MOP. With the suppository form, the mean scores were 0 for nausea, 0 for vomiting, 0 for abdominal pain, and 0 for headaches. These latter values represent scores for the entire treatment period. Clinical severity scores of psoriasis improved from a mean of 6.5 (maximum possible score = 9) at the start of the trial to a mean of 1 at its conclusion. Plasma 8-MOP levels of more than 100 ng/ml were observed in all patients who received the suppositories; in only one patient were the 8-MOP plasma levels significantly higher with the oral form than with the rectal form. CONCLUSION: Rectal suppositories of 8-MOP were associated with significantly fewer gastrointestinal side effects than the oral form of the drug; this was accomplished without compromising clinical efficacy.
Assuntos
Intestinos/efeitos dos fármacos , Metoxaleno/administração & dosagem , Estômago/efeitos dos fármacos , Dor Abdominal/induzido quimicamente , Administração Oral , Administração Retal , Cristalização , Cefaleia/induzido quimicamente , Humanos , Metoxaleno/efeitos adversos , Metoxaleno/sangue , Náusea/induzido quimicamente , Terapia PUVA , Projetos Piloto , Psoríase/tratamento farmacológico , Soluções , Supositórios , Vômito/induzido quimicamenteRESUMO
The complete profile of 8-methoxypsoralen photoadduct formation in complementary oligonucleotides (5'-GAGTATGAG and 5'-CATAC) has been determined. Equimolar solutions of the oligonucleotides were irradiated at 4 degrees C in order to stabilize the mini-double helix. Photomodified oligonucleotides were separated by reversed phase chromatography on a Vydac C4 column. Photoadduct formation favored the 5'TAT site in the 9mer over the 5'ATA site in the 5mer by a factor of two. Split-dose studies showed that the monoadducts formed on GAGTATGAG were preferentially converted to cross-links by an additional UVA exposure.