Related Experiment Videos

Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose combination (FDC) formulation

C J Shishoo1, S A Shah, I S Rathod

  • 1Department of Quality Assurance, L.M. College of Pharmacy, PO Box 4011, Navrangpura, 380 009, Ahmedabad, India.

International Journal of Pharmaceutics
|September 29, 2001
PubMed

Insights

The bioavailability of rifampicin (RIF) is significantly reduced when combined with isoniazid (INH) in fixed-dose combination (FDC) capsules. This suggests RIF stability issues in the stomach may impact FDC efficacy.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pharmaceutical Formulation and Stability

Background:

  • Fixed-dose combination (FDC) formulations are crucial for tuberculosis treatment adherence.
  • Rifampicin (RIF) and isoniazid (INH) are key anti-tuberculosis drugs often co-administered.
  • Potential drug-drug interactions and formulation stability issues can impact therapeutic efficacy.

Purpose of the Study:

  • To compare the bioavailability of RIF from a single-component RIF capsule versus a RIF-INH FDC capsule.
  • To investigate the pharmacokinetic profile of RIF and its metabolite, 25-Desacetylrifampicin (25-DAR).
  • To identify potential reasons for reduced RIF bioavailability in FDC formulations.

Main Methods:

  • A single-dose, two-treatment, two-period cross-over study involving six healthy male volunteers.
  • Development and validation of a High-Performance Thin-Layer Chromatography (HPTLC) method for quantifying RIF and 25-DAR in urine.
  • Calculation and statistical comparison of pharmacokinetic parameters including AUC and peak excretion rates.

Main Results:

  • A significant decrease in RIF bioavailability was observed from the RIF-INH FDC capsules (approximately 32% for RIF and 28% for 25-DAR).
  • Urinary excretion data indicated reduced drug availability in the FDC group.
  • Statistical analysis (ANOVA, 90% CI) confirmed the significant difference in bioavailability.

Conclusions:

  • The formulation of RIF-INH FDC capsules leads to reduced RIF bioavailability, likely due to instability in the acidic gastric environment.
  • The interaction between RIF and INH in the FDC formulation may cause RIF decomposition.
  • Reconsideration of RIF-INH FDC formulation is urgently needed to ensure drug stability and therapeutic effectiveness.

Related Concept Videos

Bioavailability: Influencing Factors01:22

Bioavailability: Influencing Factors

Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Modified-Release Drug Delivery Systems: Bioavailability01:30

Modified-Release Drug Delivery Systems: Bioavailability

Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
Dosage Regimen: Fixed Dose01:01

Dosage Regimen: Fixed Dose

Fixed-dose regimens are a common approach to administer drugs to achieve and maintain desired levels of the drug in the body. In this dosing strategy, a specific amount of medication is given at regular intervals, often multiple times a day, to ensure a consistent drug concentration in the bloodstream.
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...