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Characterization of Nelfinavir (NFV)-Associated Diarrhea: Secretory Versus Osmotic A. ANDRADE1*, C. SEARS1, P. RUFO2, W. LENCER2, and C. FLEXNER1.
1Johns Hopkins Univ., Baltimore, MD; and 2Children's Hosp., Boston, MA
Background: Diarrhea is a common complication of NFV therapy.
The mechanism of this toxicity is poorly understood.
Methods: We evaluated 5 HIV+ patients who were on NFV for ; >1
month and reported diarrhea for >4 weeks. Entry criteria included
stool output >300g/24hrs and absence of enteric pathogens or other
conditions causing diarrhea. Patients were hospitalized for 48 hrs and
placed on a lactose-free diet. A 48-hr stool collection was analyzed for
electrolytes, osmolality, osmotic gap, pH, and weight. Diarrhea was classified
as either secretory (stool weight >1kg/24 hrs, osmotic gap <50
mOsm/kg, and fecal Na and Cl >30 and 15 mEq/l respectively) or osmotic
(stool weight <500g/24 hrs, osmotic gap >50 mOsm/kg, and fecal
Na and Cl <30 and 15 mEq/l respectively).
In vitro studies on the human intestinal cell line T84 showed that NFV
10-50 µM increased physiologic levels of chloride secretion, the primary
transport event causing secretory diarrhea in humans.
Conclusions: Fecal electrolytes and osmotic gap were most suggestive
of a secretory mechanism, consistent with in vitro results, Four of five
subjects had an approximate 50% reduction in stool weight while hospitalized,
possibly secondary to the controlled diet. A better understanding of this
condition may lead to treatments that minimize NFV associated diarrhea.
Key Words: diarrhea, mechanism, nelfinavir
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