Saudi Journal of Kidney Diseases and Transplantation

: 2009  |  Volume : 20  |  Issue : 4  |  Page : 666--667

Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients

Driss El Kabbaj1, Mohammed Aatif1, Leila Ait Moussa2, Chems Eddoha Khassouani2, Zouhir Oualim1,  
1 Service of Nephrology, Haemodialysis and Kidney Transplantation, Military Hospital Mohammed V Rabat, Morocco
2 Laboratory of Toxicology, Centre Anti Poison, National Institute of Hygiene, Rabat, Morocco

Correspondence Address:
Driss El Kabbaj
Service of Nephrology, Haemodialysis and Kidney Transplantation, Military Hospital Mohammed V Rabat

How to cite this article:
El Kabbaj D, Aatif M, Moussa LA, Khassouani CE, Oualim Z. Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients.Saudi J Kidney Dis Transpl 2009;20:666-667

How to cite this URL:
El Kabbaj D, Aatif M, Moussa LA, Khassouani CE, Oualim Z. Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2022 Jul 6 ];20:666-667
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Full Text

To the Editor

Tuberculosis remains a major public health pro­blem in the developing world, and the immune compromised patients receiving dialysis the­rapy are known to be at increased risk of tuber­culosis and occur primarily in extra-pulmonary sites. Isoniazid (INH), the hydrazide of isonico­tinic acid, is the primary drug prescribed for the treatment of active tuberculosis and the prophy­laxis of tuberculosis exposure. Mild, reversible hepatotoxicity is the most common adverse drug reaction associated with therapeutic do­sages. Acute neurologic toxicity associated with overdose, however, may be fatal if not recog­nised and treated promptly. [1],[2],[3],[4],[5],[6] We therefore measured INH levels in hemodialysis who were prescribed antituberculous therapy and predict the starting dose to avoid side effects.

In 40 hemodialysis patients 69 dosages of Iso­niazid were administered. INH concentration was measured at 3 and 6 hours after the single dose (5 mg/kg) intake and before a hemodia­lysis session by high-performance liquid chro­matography (HPLC) method. The adjustment of Isoniazid dosage was done according to the serum concentration of Isoniazid between 1 to 2 µg/mL that was converted to dosage in mg/kg by the Vivien method. [10]

The average concentration of Isoniazid in this population was 3.13 (0-13.5) µg/mL and the average adjusted dose was 2.75 (0.63-17.68) mg/kg.

The hepatic metabolism of Isoniazid is by N­acetyltransferase, this acetylation is monitored by a genetic polymorphism, the rapid acety­lators have failure in achieving adequate drug levels and therefore treatment failure, while slow acetylators have more side effects. The mean plasma half-life values of isoniazid do­cumented in previous studies was 1.54 ± 0.31 in normal subjects and 3.68 ± 0.59 hours in pa­tients with chronic renal failure. [7] The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepa­tic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected. The decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acety­lation of isoniazid. [7] The hemodialysis proce­dure decreases INH levels by 73% in less than 5 hours [8] and the isoniazid clearance is 124 mL/ min. [9] No author advised a therapeutic adap­tation of the Isoniazid in the hemodialysis pa­tients, even the recommendations of the Ame­rican Society of Pulmonology, [11] while our study demonstrates that the average dose advised (2.7 mg/kg) in our population is lower than the dose recommended by the various authors (5 mg/kg). In conclusion, our study demonstrates that INH dose should be 2.5 mg/kg in the hemodialysis patients and could be confirmed by the measurement of plasma concentration to avoid its side effects which may be severe and frequent.


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