Bioavailability of Three Isoniazid Formulations

Sved, S.; McGilveray, I.J.; Beaudoin, Nicole

doi:10.1002/jps.2600661228

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…The problems associated with the use of the concentrate mixed with feed included frequently undetectable INH concentrations (12 of 23 administrations yielded undetectable serum concentrations), highly variable C max , some prolonged absorption, and flat serum concentration vs. time curves suggestive of slow and incomplete drug delivery. This may have been caused by the co-ingestion of the feed, loss of INH from the surface of the feed because of manipulation by the elephants prior to ingestion, prolonged feeding periods, and possible inactivation of INH through interaction with glucose contained in molasses (Sved et al, 1977). Nevertheless, several high concentrations were observed at 6 h postdose in some elephants suggesting a further study with prolonged sampling schedule may be warranted.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

Maslow

Mikota

Zhu

et al. 2005

Vet Pharm & Therapeutics

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We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

Maslow

Mikota

Zhu

et al. 2005

Vet Pharm & Therapeutics

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“…80% within 45 min in 900 mL 0.01 N HCl at 378C in the basket apparatus at 100 rpm. 20 In the Gelber study 39 and in the Sved study, 40 all formulations successfully passed an in vivo BE study and also complied with the in vitro dissolution criteria, see above, although the tests were not fully identical to the current USP specification.…”

Section: Dissolutionmentioning

confidence: 97%

“…Isoniazid can interact with saccharides such as lactose, with consequences for the BA. 23,31 The extent of this reaction seems to depend on the amount of excipients present in the formulation: in the Sved study, 40 two of the three isoniazid formulations tested contained lactose in amounts of less than 4% and no significant differences were found in the BA of the three products. Moreover, Isoniazide 200 PCH tabletten 200 mg 1 , which has a MA in NL, contains lactose, see Table 2.…”

Section: Risk For Bioinequivalence Caused By Excipients And/or Manufamentioning

confidence: 99%

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Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Isoniazid**A project of the International Pharmaceutical Federation FIP, Groupe BCS, www.fip.org/bcs.

Becker

Dressman

Amidon

et al. 2007

Journal of Pharmaceutical Sciences

106

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Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing isoniazid as the only active pharmaceutical ingredient (API) are reviewed. Isoniazid's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Isoniazid is "highly soluble" but data on its oral absorption and permeability are inconclusive, suggesting this API to be on the borderline of BCS Class I and III. For a number of excipients, an interaction with the permeability is extreme unlikely, but lactose and other deoxidizing saccharides can form condensation products with isoniazid, which may be less permeable than the free API. A biowaiver is recommended for IR solid oral drug products containing isoniazid as the sole API, provided that the test product meets the WHO requirements for "very rapidly dissolving" and contains only the excipients commonly used in isoniazid products, as listed in this article. Lactose and/or other deoxidizing saccharides containing formulations should be subjected to an in vivo BE study.

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“…In current therapy, the most effective drug against tuberculosis is isoniazid (INH), which is usually administered in combination with other drugs (I). Formulating combinations usually involves optimizing of the drug release from their dosage forms to guard against physical incompatibility and inadequate bioavailability (2). Indeed, the bioavailability of iso-niazid combined with rifampicin or with pyrazinamide showed no significant interaction between these drugs (3).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Thiacetazone Solubility by Isoniazid in Aqueous Solutions

Zughul¹,

Omari²,

Badwan³

1996

Drug Development and Industrial Pharmacy

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The aqueous solubility of thiacetazone was enhanced in the presence of different concentrations of isoniazid. The nature of this solubilization was investigated by measuring some physicochemical properties of isoniazid in water. Slight suqace activity and conductance were observed. Osmotic pressure and partition coeflcient measurements indicated that isoniazid dimerizes in aqueous solutions and were used to obtain and verify the dimerization constant. There was no evidence of higher oligomer formation in concentrations lower than 1.0 M. This excluded the possibility of solubilization by aggregate formation. Citric and glutaric acids in the presence of isoniazid were found to increase thiacetazone solubility as a function of the acid concentration and structure.

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Bioavailability of Three Isoniazid Formulations

Cited by 8 publications

References 14 publications

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Isoniazid**A project of the International Pharmaceutical Federation FIP, Groupe BCS, www.fip.org/bcs.

Enhancement of Thiacetazone Solubility by Isoniazid in Aqueous Solutions

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