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Clodronate kinetics and dynamics.

K A Conrad, S M Lee

    Clinical Pharmacology and Therapeutics
    |July 1, 1981
    PubMed
    Summary
    This summary is machine-generated.

    Clodronate disodium (Cl2MDP) is primarily excreted by the kidneys in men, with no significant impact on renal function. This bisphosphonate affects serum phosphate levels but not calcium or other key renal markers.

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    Area of Science:

    • Pharmacology
    • Nephrology
    • Biochemistry

    Background:

    • Bisphosphonates, such as Clodronate disodium (Cl2MDP), are used to treat bone diseases.
    • Understanding the pharmacokinetic profile and renal effects of Cl2MDP is crucial for its safe and effective clinical application.

    Purpose of the Study:

    • To investigate the pharmacokinetics of intravenously administered Clodronate disodium in healthy adult males.
    • To assess the effects of Clodronate disodium on renal function and serum electrolyte levels.

    Main Methods:

    • Intravenous administration of Clodronate disodium (Cl2MDP) at doses of 3, 6, and 10 mg/kg to six healthy adult males.
    • Measurement of pharmacokinetic parameters including volume of distribution, elimination rate constant, and total body clearance.
    • Assessment of renal clearance, urinary excretion, serum electrolytes (phosphate, calcium, sodium), uric acid, creatinine clearance, and renal concentrating ability.

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    Main Results:

    • Clodronate disodium exhibited consistent pharmacokinetic parameters across the tested doses, with a volume of distribution around 0.25-0.30 L/kg and total body clearance around 0.10 L/kg/hr.
    • Renal clearance accounted for 73% of total body clearance, with 73% of the drug excreted unchanged in urine within 24 hours.
    • A transient decrease in serum phosphate (~13%) was observed, particularly at the 10 mg/kg dose, associated with a fall in fractional phosphate excretion. No significant changes were noted in calcium, sodium, uric acid, creatinine clearance, or renal concentrating ability.

    Conclusions:

    • Clodronate disodium is predominantly eliminated by the kidneys in humans following short-term intravenous administration.
    • Clodronate disodium does not appear to significantly impair renal function, as evidenced by stable creatinine clearance and concentrating ability.
    • The observed transient hypophosphatemia suggests a potential interaction with phosphate metabolism, warranting further investigation in specific patient populations.