Determination of the acetylator phenotype from the ratio of the urinary excretion of acetylisoniazid to acid-labile isoniazid: a study in finnish lapland

Ellard, G. A.; Gammon, Patricia T.; Tiitinen, Hannu

doi:10.1016/0041-3879(73)90025-1

Cited by 20 publications

(19 citation statements)

References 20 publications

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“…In the method originally devised by Jenne (1960), and extensively employed by Tiitinen (1969) and her coworkers (1973) (Barclay et al, 1953), Evans et al, (1960) showed that much simpler classification methods could be devised, based on a single plasma determination 6 h after an oral dose of 10 mg/kg. Other methods included are based on the ratio of acetyl INH to INH in urine obtained during certain time-period (Venkataraman et al, 1972;Ellard et al, 1973) and ratio of acetyl INH to INH in plasma at a fixed time point (Ellard & Gammon, 1976 Olson et al (1977). Fluorometry was done with a Hitachi MPF-4 Fluorescene Spectrophotometer, at 386 (excitation) and 476 nm (emission) wavelength, with the dynode voltage at 700 V and all slit widths at 10 nm.…”

Section: Acetylatorphenotypingmentioning

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

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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.

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Section: Acetylatorphenotypingmentioning

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

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“…mean 0.665 + 0.039) 1/kg in the ten rapid acetylators, while it was 0.324 1/kg in the patient, which was found within the lowest iange of the rapid acetylators examined. Such a small value has also been involved in the data reported by other investigators (Jenne, MacDonald & Mendoza, 1961;Ellard, Gammon & Tiitinen, would differ between slow and rapid acetylators (Weber & Hein, 1979 In this case it is probably suggested that the hydralazine administration was causally correlated to the aetiology of the development of peripheral neuropathy according to the definition of cause-effect relationship between a drug and its adverse reaction proposed by Karch & Lasagna (1975). This is the first report in a slow acetylator residing in the region where rapid acetylators highly predominate in general population (Sunahara et al, 1961;Lunde et al, 1977;Weber & Hein, 1979).…”

mentioning

confidence: 60%

Hydralazine‐induced peripheral neuropathy seen in a Japanese slow acetylator patient.

Tsujimoto¹,

Horai²,

Ishizaki³

et al. 1981

Brit J Clinical Pharma

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“…Isoniazid and pyrazinamide were chosen as suitable drugs for comparison since previous studies had indicated that they readily penetrate most body tissues. Thus both drugs are excellently absorbed in man, appear to be distributed throughout the total body water, are almost completely reabsorbed by the kidney, readily penetrate into the cerebrospinal fluid (CSF) and are highly effective against intracellular infections of Mycobacterium tuberculosis (Peters, Miller & Brown, 1965;Ellard, 1969;Gelber, Jacobsen & Levy, 1969;Weiner & Tinker, 1972;Ellard, Gammon & Tiitinen, 1973; Forgan-Smith, Ellard, Newton & Mitchison, 1973;Fox & Mitchison, 1975;Ellard & Gammon, unpublished observa-tions). However, there appears to be very little knowledge concerning the penetration of these drugs, or indeed of other chemotherapeutic agents, into peripheral nerves.…”

Section: Introductionmentioning

confidence: 99%

The Penetration of Dapsone, Rifampicin, Isoniazid and Pyrazinamide Into Peripheral Nerves

Allen

Ellard

Gammon

et al. 1975

British J Pharmacology

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Determination of the acetylator phenotype from the ratio of the urinary excretion of acetylisoniazid to acid-labile isoniazid: a study in finnish lapland

Cited by 20 publications

References 20 publications

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

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

Hydralazine‐induced peripheral neuropathy seen in a Japanese slow acetylator patient.

The Penetration of Dapsone, Rifampicin, Isoniazid and Pyrazinamide Into Peripheral Nerves

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