Cephradine excretion in humans with pH-altered urine

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Urinary pH Manipulation

Background:

• Urinary pH can influence the absorption and excretion of certain drugs.
• Cephradine is an antibiotic with potential pH-dependent pharmacokinetic properties.

Purpose of the Study:

• To investigate the effect of altered urinary pH on the pharmacokinetics of cephradine.
• To determine if urinary pH manipulation impacts cephradine absorption and elimination.

Main Methods:

• Random crossover study design.
• Ten healthy male participants.
• Pretreatment with ammonium chloride or sodium bicarbonate to modify urinary pH.
• Administration of a single 1-Gm dose of cephradine (oral or intravenous).
• Analysis of pharmacokinetic parameters including terminal phase rate constant, peak concentration, and area under the curve (AUC).

Main Results:

• No significant changes in terminal phase rate constant, peak concentration time, or magnitude.
• High total recovery (>90%) observed when cephradine degradation was minimal.
• Significant reduction in AUC noted in pre-alkalinized subjects.
• Significant reduction in AUC observed for orally administered cephradine.
• No significant cephradine trapping in the excretory pathway.

Conclusions:

• Urinary pH alteration does not significantly impact cephradine's elimination rate or peak concentration.
• Oral absorption and overall bioavailability of cephradine may be reduced under conditions of urinary alkalization.
• Further research is warranted to elucidate the mechanisms behind the reduced AUC in specific conditions.