Pharmacokinetics of Diethylcarbamazine after Single Oral Dose at Two Different Times of Day in Human Subjects

Abstract

In most Wuchereria bancrofti and Brugia malayi infections, the microfilaria are found in the blood in greatest number between 10 p.m. and 2 a.m., indicating that chronotherapy may be beneficial in treating such infections. This study reports the influence of time of administration on the pharmacokinetics of diethylcarbamazine (DEC) in healthy volunteers. The study was conducted in 12 healthy volunteers by administering a 150 mg single oral dose of diethylcarbamazine citrate at 0600 or 1800 h in a balanced crossover design with the approval of an institutional ethics committee. The subjects fasted for about 10 hours before and 3 hours after drug treatment. Blood samples were collected at predetermined time intervals, and the drug content in the serum was estimated using HPLC with an electrochemical detector. Pharmacokinetic analysis was performed using noncompartmental methods employing WinNonlin (version 3.1), and the means of various pharmacokinetic parameters were compared for any dosing time-related changes using a paired t-test at a probability level of 95%. The mean +/- SD values of pharmacokinetic parameters of DEC for the treatments at 0600 versus 1800 h were as follows: Cmax, 500+/-227 versus 637+/-401 ng/ml; tmax, 2.3+/-0.7 versus 2.7+/-1 h; Ka, 2.23+/-0.72 versus 1.96+/-0.97 h(-1); t1/2, 14.6+/-6.7 versus 11.4+/-4.9 h; AUC0-t, 5,334+/-1,853 versus 6,901+/-4,203 ng x h/ml; AUC0-infinity, 5,840+/-1,922 versus 7,220+/-4,205 ng x h/ml; CL/F, 36,058+/-19,011 versus 32,189+/-25,293 ml/h/kg; Vd/F, 570+/-225 versus 533+/-447 L; and MRT 17.7+/-5.9 versus 15.3+/-5.2 h. None of the parameters was significantly changed (p > 0.05) as a function of time of administration.

Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

“…In the present work, the choice of using 5 μg/ml as the minor concentration of DEC was based on classical pharmacological studies (Hawking et al 1948). It represents about four times higher than those observed on plasma concentration as indicated by recent reports (Bolla et al 2002). Positive nuclei were found in microfilariae DEC-treated by TUNEL analyses confirming the ultrastructural evidences of apoptosis.…”

“…It is important to note that the dose utilized by these researchers was half of those frequently used in clinical procedures, which is 6 mg/kg (Bolla et al 2002). In the present work, the choice of using 5 μg/ml as the minor concentration of DEC was based on classical pharmacological studies (Hawking et al 1948).…”

LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: Application to a clinical pharmacokinetic study

“…Similarly, bioanalytical methods are available for determination of DEC [ [15] , [16] , [17] , [18] ], however limitations in these methods still preclude their implementation in PK studies. Lee et al developed a gas chromatographic method with a LLOQ of 10 ng/mL with a required sample volume of 1 mL of plasma using a NPD detector [ 18 ].…”

Changes in mouse Leydig cells ultrastructure and testosterone secretion after diethylcarbamazine administration

“…Horii and Aoki (1997) described the plasma level of 200 mg/kg of DEC in rats by using a gas-liquid chromatograph equipped with a flame ionization detector, registering values of 30 mg/ml at 30-60 min after injection, decreasing rapidly to 1.5 mg/ml after 4 h. This study indicated that in rats, the oral administration of 200 mg/Kg of DEC presented $1.5 h as a mean elimination of half-life. On the other hand, in humans, after DEC oral administration of 150 mg, the plasma concentration achieves values of 0.5 mg/ml (Bolla et al, 2002). Since the clearance of this compound is higher in rodents than humans, in the present study we utilized a higher dose of DEC, as described elsewhere (Horii and Aoki, 1997).…”