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Indinavir crystallization around the loop of Henle: experimental evidence
J P Dieleman1, S Salahuddin, Y S Hsu
1Pharmaco-Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Center (EMCR), Rotterdam, The Netherlands.
Journal of Acquired Immune Deficiency Syndromes (1999)
|October 2, 2001
Summary
Indinavir (IDV) crystallization likely occurs in the loop of Henle at plasma concentrations as low as 8 mg/L. Increased hydration prevents lower urinary tract crystallization but not in the loop of Henle.
Area of Science:
- Nephrology
- Pharmacology
- Crystallography
Background:
- Indinavir (IDV) is an antiretroviral medication used to treat HIV/AIDS.
- Intrarenal crystallization of IDV can lead to kidney damage.
- Understanding the conditions for IDV crystallization is crucial for patient safety.
Purpose of the Study:
- To identify the specific site within the nephron where indinavir (IDV) crystallization occurs.
- To determine the plasma IDV concentration threshold for intrarenal crystallization.
Main Methods:
- In vitro crystallization experiments were conducted using IDV solutions.
- Simulated physiological conditions of the nephron, including pH and ionic strength, were used.
- IDV concentrations were titrated to identify crystallization points.
Main Results:
- IDV crystallized at 200 mg/L under proximal tubule conditions (pH 6.7, 200 mM ionic strength).
- IDV crystallized at 125 mg/L under loop of Henle conditions (pH 7.4, 200 mM ionic strength).
- This corresponds to a plasma IDV concentration of 8 mg/L for loop of Henle crystallization.
Conclusions:
- Indinavir (IDV) crystallization is most probable in the loop of Henle.
- Crystallization may initiate at plasma IDV concentrations as low as 8 mg/L.
- Increased hydration aids in preventing lower urinary tract crystallization but not in the loop of Henle.