Effect of latamoxef on platelet function and prothrombin time in partially nephrectomized rats

Area of Science:

• Pharmacology
• Nephrology
• Biochemistry

Background:

• Antibiotics containing N-methyltetrazolethiol (NMTT), such as latamoxef, have been associated with hypoprothrombinemia.
• The impact of renal impairment and vitamin K status on the safety profile of these antibiotics requires further investigation.

Purpose of the Study:

• To investigate the effect of latamoxef on prothrombin time and platelet aggregation in rats with varying degrees of nephrectomy and vitamin K intake.
• To determine if NMTT-containing antibiotics can induce hypoprothrombinemia in compromised renal function and vitamin K deficiency.

Main Methods:

• Rats underwent 75% or 90% nephrectomy and were fed either a vitamin K-sufficient or deficient diet.
• Latamoxef was administered intravenously daily for 8 days.
• Prothrombin time and ADP-induced platelet aggregation were measured.

Main Results:

• Latamoxef's half-life was prolonged, and plasma concentrations of latamoxef and NMTT increased in nephrectomized rats.
• Prothrombin time increased dose-dependently in vitamin K-deficient nephrectomized rats, with greater increases in 90% nephrectomized animals.
• Platelet aggregation was not significantly affected by latamoxef at the tested doses.

Conclusions:

• NMTT-containing antibiotics do not cause hypoprothrombinemia in partially nephrectomized rats with adequate vitamin K intake.
• Vitamin K deficiency and increased renal failure enhance the manifestation of hypoprothrombinemia by increasing drug concentrations.
• Platelet aggregation is not significantly impacted by latamoxef under these experimental conditions.