Isoniazid

Structural formula
General
Non-proprietary name	Isoniazid
other names	Isonicotinic hydrazide (INH); Pyridine-4-carbohydrazide;
Molecular formula	C 6 H 7 N 3 O
External identifiers / databases
EC number	200-214-6
ECHA InfoCard	100,000,195
PubChem	3767
DrugBank	DB00951
Wikidata	Q423169
Drug information
ATC code	J04 AC01 ; J04 AC51 ; J04 AM02 ;
Drug class	antibiotic
properties
Molar mass	137.14 g · mol -1
Physical state	firmly
Melting point	169-172 ° C
solubility	moderate in water (125 g / l at 20 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: 301 + 312 + 330
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Isoniazid , also Isonicotinsäurehydrazid , engl. isonicotinic acid hydrazide, abbreviated INH , is a bactericidal antibiotic that is mainly used in combination with rifampicin to treat tuberculosis . In HIV patients, prophylactic treatment with isoniazid can reduce the number of tuberculosis cases and also the overall deaths.

Isoniazid was synthesized in 1912 by Meyer and Malley at the University of Prague. The antibiotic effect was only recognized after the Second World War . In the Hoffmann-La Roche laboratories in Nutley , New Jersey, H. Herbert Fox and co-workers developed isoniazid and the variant iproniazid ready for the market. Even Gerhard Domagk worked on these substances for Bayer AG .

In Mycobacterium tuberculosis , the tuberculosis bacterium, isoniazid is converted to isonicotinic acid radical by the enzyme catalase / peroxidase (KatG) , which attaches to the NADH molecule that is permanently bound to the reductase InhA, which is essential for mycolic acid synthesis is inhibited. Resistance, the newly developed the bacterium relate exclusively to the katG - gene and thus the activation of isoniazid.

Medication with INH can lead to disorders of the central nervous system, gastrointestinal disorders or allergies. Intrahepatic jaundice can also occur as a side effect. Pyridoxine (vitamin B ₆ ) can be given as a concomitant preparation to reduce the side effects on the nervous system. In connection with alcohol it can lead to a temporary alcohol intolerance (chemical alcohol intolerance).

INH is mostly administered orally and it has a very good bioavailability (≈ 90%). It is 75% acetylated in the liver . In addition, it is enzymatically hydrolyzed to isonicotinic acid . Isoniazid and its metabolites are mainly excreted renally .

Trade names

Monopreparations

INH (A), Isozid (D), Rimifon (CH), Tebesium (D)

Combination preparations

Iso-Eremfat (D), Isozid-comp. (D), Rifater (D, A, CH), Rifinab (D), Rifinah (CH), Rifoldin (A), Rimactazid (D), Rimstar (CH), Tebesium Duo / Trio (D)

Individual evidence

↑ ^a ^b Isoniazid data sheet (PDF) from Merck , accessed on January 19, 2011.

↑ ^a ^b Entry on isonicotinic acid hydrazide in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .

↑ Mutschler, drug effects, 9th edition, Wissenschaftliche Verlagsgesellschaft Stuttgart, 2008, p. 849 ISBN 978-3-8047-1952-1

↑ Betina Durovni, Valeria Saraceni, Lawrence H Moulton, Antonio G Pacheco, Solange C Cavalcante, Bonnie S King, Silvia Cohn, Anne Efron, Richard E Chaisson, Jonathan E Golub: Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomized trial. In: The Lancet Infectious Diseases. 2013, S., doi : 10.1016 / S1473-3099 (13) 70187-7 .

↑ DA Rozwarski, GA Grant et al. a .: Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. In: Science Volume 279, Number 5347, January 1998, pp. 98-102. PMID 9417034 .

↑ CE Cade, AC Dlouhy et al. a .: Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: catalase, peroxidase, and INH-NADH adduct formation activities. In: Protein science: a publication of the Protein Society Volume 19, Number 3, March 2010, pp. 458-474. doi : 10.1002 / pro.324 . PMID 20054829 . PMC 286627 (free full text).

[merck-1] Isoniazid data sheet (PDF) from Merck , accessed on January 19, 2011.

[GESTIS-2] Entry on isonicotinic acid hydrazide in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .

[3] Mutschler, drug effects, 9th edition, Wissenschaftliche Verlagsgesellschaft Stuttgart, 2008, p. 849 ISBN 978-3-8047-1952-1

[DOI10.1016/S1473-3099(13)70187-7-4] Betina Durovni, Valeria Saraceni, Lawrence H Moulton, Antonio G Pacheco, Solange C Cavalcante, Bonnie S King, Silvia Cohn, Anne Efron, Richard E Chaisson, Jonathan E Golub: Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomized trial. In: The Lancet Infectious Diseases. 2013, S., doi : 10.1016 / S1473-3099 (13) 70187-7 .

[PMID9417034-5] DA Rozwarski, GA Grant et al. a .: Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. In: Science Volume 279, Number 5347, January 1998, pp. 98-102. PMID 9417034 .

[PMID20054829-6] CE Cade, AC Dlouhy et al. a .: Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: catalase, peroxidase, and INH-NADH adduct formation activities. In: Protein science: a publication of the Protein Society Volume 19, Number 3, March 2010, pp. 458-474. doi : 10.1002 / pro.324 . PMID 20054829 . PMC 286627 (free full text).