Quantitative determination of hydrazines berived from isoniazid in patients. I.

Noda, Atsuko; Goromaru, Tsuyoshi; Matsuyama, Kenji; Sogabe, Keizo; Hsu, Kuang-Yang; Iguchi, Sadao

doi:10.1248/bpb1978.1.132

Cited by 32 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The intact INH and its metabolites in urine (acetyl INH, monoacetylhydrazine, diacetylhydrazine, and free hydrazine) were analyzed by gas chromatography and gas chromatography-mass spectrometry. The details are described in the previous reports by Iguchi et a1 (27) and Noda et a1 (28). Briefly, unchanged INH, acetyl INH, and diacetylhydrazine were assayed by using benzoic acid hydrazide (BAH) as the internal standard on Shimazu Model GC-4BM-PF gas chromatograph equipped with a hydrogen flame ionization detector.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Acetylator phenotype and metabolic disposition of isoniazid in japanese patients with systemic lupus erythematosus

Ishizaki

Horai

Koya

et al. 1981

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

TAKASHI ISHIZAKI, YUKIO HORAI, GYOICHI KOYA, KENJI MATSUYAMA, and SADAO IGUCHI Acetylator phenotype and metabolic disposition of isoniazid (INH) were studied in 19 Japanese (a population shown to be 11.5% slow acetylators) patients with spontaneous systemic lupus erythematosus (SLE) and 19 healthy controls. Subjects with the elimination half-life (t1/2) of INH of 2.0 hours or less were considered rapid and those of 2.2 hours or more were slow acetylators. Results of phenotyping showed that 17 of 19 SLE patients were rapid, 1 slow, and 1 indeterminate, whereas 18 of the controls were rapid and 1 indeterminate. When phenotyped according to another reported antimode (107 or 110 minutes), 3 of the patients and 2 of the controls were slow and the remainder were all rapid acetylators. The distribution of INH t1/2, acetyl I N H to INH ratios in urine and plasma, and hydrazine compounds in urine measured with gas chromatography----_

show abstract

Section: Methodsmentioning

confidence: 99%

“…Monoacetylhydrazine and free hydrazine could be successfully determined by mass fragmentography using I5N-hydrazine as the internal standard (27,28). IsN-hydrazine and benzaldehyde were added to urine sample to form I-acetyl-2-benzyliden-hydrazine (ABH), benzalazine, and 15N-benzalazine.…”

Section: Methodsmentioning

confidence: 99%

Acetylator phenotype and metabolic disposition of isoniazid in japanese patients with systemic lupus erythematosus

Ishizaki

Horai

Koya

et al. 1981

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…The intact INH and its metabolites in urine, acetyl INH, mono-acetylhydrazine, diacetylhydrazine and free hydrazine, were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The details are described in the previous reports by Noda et al, (1978 (Fox & Gibas, 1953;Turner, 1947). Briefly, unchanged INH, acetyl INH and diacetylhydrazine were assayed by using BAH as the internal standard on a glass column (1 m x 3 mm, i.d.)…”

Section: Analysis Of Urinary Metabolitesmentioning

confidence: 99%

“…Monoacetylhydrazine and free hydrazine could be successfully determined by the mass fragmentography using [15N]-hydrazine as the internal standard (Noda et al, 1978;Iguchi et al, 1977). ['5N]-hydrazine and benzaldehyde were added to urine samples (pH 6.0) to form l-acetyl-2-benzylidenhydrazine (ABH), benzalazine and ['N]-benzalazine.…”

Section: Analysis Of Urinary Metabolitesmentioning

confidence: 99%

Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

Horai¹,

Ishizaki²,

Sasaki³

et al. 1982

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 Plasma levels of isoniazid (INH) and acetyl INH in plasma were measured with a spectrofluorometric method, and INH and its metabolites (acetyl INH, mono‐acetylhydrazine, diacetylhydrazine and free hydrazine) excreted in urine were measured with a gas chromatography‐ mass spectrometry, respectively, after an oral dose of INH 10 mg/kg in 19 Japanese patients with idiopathic systemic lupus erythematosus (SLE) and in the same number of healthy controls. 2 When phenotyped according to various methods previously reported, 16 to 18 of the SLE and 17 to 19 of the control group were rapid acetylators. Regardless of the phenotyping methods applied, the distribution of acetylator phenotype of SLE patients was not significantly different from the control group or from the data previously reported among normal Japanese population. 3 By phenotyping our subjects with an INH T 1/2 of 110 min or less as rapid acetylators, and more slow acetylators, 3 of SLE patients and 2 of the controls were slow, while the remainder were all rapid. When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration‐time data and the mean values for the 24‐h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups. 4 The distribution of INH T 1/2, acetyl INH to INH ratios in plasma and urine, values in urine for log10 (diacetylhydrazine to monoacetylhydrazine) and for diacetylhydrazine to INH or acetyl INH was similar between the two groups except for one patient who was definitely classified as a slow acetylator regardless of whichever phenotyping methods were used. The excretory patterns of hydrazine compounds reflect, in general, the inactivating ability of INH in each individual. 5 The data suggest that phenotyping by using plasma samples is, in general, better than by using urine samples. The plasma T 1/2 alone is the most satisfactory criterion. 6 We conclude that neither INH disposition nor phenotype distribution assessed by the reported methods using INH as the test compound are altered in idiopathic SLE, and that a search for racial and/or geographical factor(s) likely to result in autoimmune disease may give a clue to the pathogenesis in addition to further exploration for the possible interrelation between idiopathic SLE and genetic slow acetylation.

show abstract

“…Hydrazine is also a metabolite of the two widely used drugs, isoniazid (Noda et al 1978;Blair et al 1985) and hydralazine (Timbrell and Harland 1979). Hydrazine itself has been used in the treatment of weight loss in terminal cancer patients (Gold 1987).…”

Section: Introductionmentioning

confidence: 99%

Proton NMR spectroscopic studies on the metabolism and biochemical effects of hydrazine in vivo

Sanins

Timbrell

Elcombe³

et al. 1992

Arch Toxicol

View full text Add to dashboard Cite

The metabolism and disposition of hydrazine and its effects on endogenous metabolites has been studied in rats by the use of high resolution proton NMR spectroscopy of urine. Several metabolites of hydrazine were detected, notably acetyl- and diacetylhydrazine and a cyclised metabolite which results from a hydrazone formed from 2-oxoglutarate and hydrazine. Effects of hydrazine on endogenous metabolites in urine and plasma were also observed; notably a dose-related increase in urinary taurine, a dose-related increase in urinary and plasma lactate, increases in urinary alpha-alanine, beta-alanine, methylamine and a decrease in urinary 2-oxoglutarate. This study has indicated the utility of using high resolution proton NMR spectroscopy to analyse urine for both metabolites and endogenous compounds after exposure of animals to toxic substances.

show abstract

Quantitative determination of hydrazines berived from isoniazid in patients. I.

Cited by 32 publications

References 16 publications

Acetylator phenotype and metabolic disposition of isoniazid in japanese patients with systemic lupus erythematosus

Acetylator phenotype and metabolic disposition of isoniazid in japanese patients with systemic lupus erythematosus

Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

Proton NMR spectroscopic studies on the metabolism and biochemical effects of hydrazine in vivo

Contact Info

Product

Resources

About