Microsomal enzyme induction and clinical aggravation of porphyria: the evaluation of human urinary 6beta-hydroxycortisol/cortisol ratio as the index of hepatic CYP3A4 activity.
The clinical aspect of porphyria has been investigated, and it is well known that porphyrinogens such as estrogens and alcohol or other inducers of P450 isoenzymes exacerbate the porphyric state. However, there can be a delay in diagnosing porphyria and a difficulty in selecting safe medicine for it even today. A 21-year-old woman developed epilepsy, disturbance of mental state, and spastic tetraparesis during the convalescent period after acute viral encephalitis. She was diagnosed with porphyria after the fifth hospitalization. In the course of modifying her anticonvulsant regimen, the authors examined the 6beta-hydroxycortisol/cortisol ratio (6beta-OHF/F) in her urine, which can be the index of hepatic CYP3A4 activity, with electrospray ionization/mass spectrometry/mass spectrometry (ESI/MS/MS). Generalized and partial complex seizures, other neurological signs and symptoms, and laboratory data were improved after modification of her anticonvulsant regimen. This is the first report of evaluating the urinary 6beta-hydroxycortisol/cortisol ratio in a case of porphyria.
Uejima
Etsuko
E
Department of Pharmacy, Osaka University Hospital, Suita, Osaka, Japan.
Takahashi
Kyoko
K
Morisaki
Tomoko
T
Takahashi
Koichi
K
Ohno
Masako
M
Nishida
Yuko
Y
Moriya
Masayuki
M
Kaido
Misako
M
Abe
Kazuo
K
Sakoda
Saburo
S
Yanagihara
Takehiko
T
Kurokawa
Nobuo
N
Azuma
Junichi
J
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D020803:Encephalitis, Herpes Simplex / Q000150:complications; D004790:Enzyme Induction; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology; D005243:Feces / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D013058:Mass Spectrometry; D008861:Microsomes / Q000201:enzymology*; D011164:Porphyrias / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology; D011166:Porphyrins / Q000032:analysis / Q000652:urine; D011782:Quadriplegia / Q000209:etiology
D000927:Anticonvulsants; D011166:Porphyrins; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006854:Hydrocortisone