[Average steady-state plasma levels with slow release quinidine preparations]

Area of Science:

• Pharmacology and Pharmaceutics
• Drug Delivery Systems
• Clinical Therapeutics

Context:

• Quinidine is an antiarrhythmic drug with a narrow therapeutic index.
• Slow-release formulations aim to improve quinidine's therapeutic profile by reducing peak plasma concentrations and prolonging drug effect.
• Different Arabogalactane sulphate of quinidine (AGSQ) preparations (I, II, III) vary in their in vitro drug release characteristics.

Purpose:

• To compare plasma quinidine levels achieved with different AGSQ formulations (AGSQ I, II, III) and immediate-release quinidine sulphate.
• To identify the AGSQ preparation most suitable for therapeutic use based on plasma concentration profiles and safety margins.

Summary:

• In vitro studies showed AGSQ III released 100% of quinidine in 6 hours, AGSQ II released 58%, and AGSQ I released 34%.
• In vivo, AGSQ II maintained plasma quinidine levels between therapeutic and toxic ranges (1.7-3.5 µg/ml) by avoiding the sharp peaks seen with quinidine sulphate.
• AGSQ II demonstrated a longer delay to reach steady-state plasma levels (48 hours) compared to quinidine sulphate (24 hours) and AGSQ I (36 hours).

Impact:

• AGSQ II is recommended for therapeutic use due to its ability to maintain stable, safe quinidine plasma concentrations, reducing the risk of toxicity.
• A strong correlation (r=0.984) between 6-hour post-ingestion plasma levels and Cee suggests this time point is valuable for dosage adjustments.
• This study highlights the importance of formulation in optimizing drug delivery and therapeutic outcomes for quinidine.