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| Year : 2009 | Volume
: 20
| Issue : 4 | Page : 666-667 |
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| Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients |
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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
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| Date of Web Publication | 8-Jul-2009 |
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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;20:666-7 |
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 May 22];20:666-7. Available from: https://www.sjkdt.org/text.asp?2009/20/4/666/53298 |
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.
 References | |  |
| 1. | Wang HY. Encephalopathy caused by isoniazid in a patient with end stage renal disease with extra pulmonary tuberculosis. Ren Fail 2003;25 (1):135-8.  |
| 2. | Altiparmak MR, Pamuk ON, Pamuk GE, et al, Is isoniazid ototoxic in patients undergoing hemodialysis? Nephron 2002; 92(2):478-80. |
| 3. | Kocabay G. Optic neuritis and bitemporal hemianopsia associated with isoniazid treatment in end stage renal failure. Int J Tuberc Lung Dis 2006;10(12):1418-9. |
| 4. | Temmerman W, Dhondt A, Vandewoude K. Acute isoniazid intoxication: seizures, acidosis and coma. Acta Clin Belg 1999;54(4):211-6. |
| 5. | Chan KL Recurrent acute pancreatitis induced by isoniazid. Tuber Lung Dis 1994;75(5):383-5. |
| 6. | Siskind MS. Isoniazid-induced neurotoxicity in chronic dialysis patients: report of three cases and a review of the literature. Nephron 1993;64 (2):303-6. |
| 7. | Kim YG. Decreased acetylation of isoniazid in chronic renal failure. Clin Pharmacol Ther 1993;54(6):612-20. |
| 8. | Gold CH. Isoniazid pharmacokinetics in patients in chronic renal failure. Clin Nephrol 1976;6(2):365-9. |
| 9. | Malone RS. The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol. Am J Respir Crit care Med 1999;159(5 Pt 1): 1580-4. |
| 10. | Vivien J.N, Thibier R, Lepeuple A. La pharmacocinetique de l'isoniazide dans la race blanche. Rev Fr Mal Resp 1973;1:753-72. |
| 11. | ATS/CDC/IDSA. Am J Respir Crit Care Med 2003; 167:603. |
Correspondence Address:
Driss El Kabbaj
Service of Nephrology, Haemodialysis and Kidney Transplantation, Military Hospital Mohammed V Rabat
Morocco
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 19587514 
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| This article has been cited by | | 1 |
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| Wang, X. and Zhuang, J. and Xie, L. and Li, M. and Lu, Y. | | Reviews in Medical Microbiology. 2011; 22(1): 5-11 | | [Pubmed] | |
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