Protein binding and ivermectin estimations in patients with onchocerciasis

Abstract

We measured ivermectin in plasma, urine, and saliva of nine patients with onchocerciasis. The aim was to establish pharmacokinetic parameters and to assess the most facile medium for use in monitoring compliance. Binding of ivermectin to plasma proteins in vitro was also investigated. The mean (+/- SEM) plasma values for the nine subjects were as follows: weight, 66.3 +/- 2.8 kg; dose, 11.11 +/- 0.4 mg; half-life, 56.50 +/- 7.01 hours; clearance, 142.5 +/- 22.6 L/kg; volume of distribution, 9.91 +/- 2.67 L/kg; area under the plasma concentration-time curve, 1545.3 +/- 190.5 ng/ml.hr; time to reach maximum concentration, 4.7 +/- 0.5 hours; and maximum concentration, 38.2 +/- 5.8 ng/ml. Ivermectin was not detected in the urine of any of the nine subjects. Low levels were found in saliva. Blood specimens remain the only reliable biologic fluid for assessment of compliance after ivermectin oral administration. Ivermectin binds specifically to human serum albumin.

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

“…In onchocerciasis patients, with 6 mg (tablet), the volume of distribution of the area (V λ ) was 9.9 l·kg −1 and the mean residence time (MRT) was 3.7 days (16).…”

“…Such avid binding assumes great importance as the drug is administered in world areas where malnutrition and hypoalbuminemia are common, so in these patients a decrease in plasma proteins and, consequently, a higher free fraction of ivermectin could be expected. Nevertheless, acetylsalicylic acid does not interfere with ivermectin binding (16).…”

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

“…Compliance to non-observed ivermectin therapy in mass drug administration programs could be assessed through plasma concentration monitoring [88]. …”

Patterns of doramectin tissue residue depletion in parasitized vs nonparasitized lambs

“…The increased permeability of the digestive epithelium to plasma proteins in the gastrointestinal lumen reduces the half-life of plasma albumin and immunoglobulin up to 50% (Barriga 1996). Binding studies in humans and dogs showed that ivermectin bound extensively to plasma proteins (Okonkwo et al 1993), including albumin and lipoproteins (Rohrer and Evans 1990). Consequently, plasma protein leakage into the gut might have been an important factor for increasing the fecal excretion of DRM and reducing the tissue distribution of the drug in the parasitized lambs in this study.…”