Simultaneous measurement of proguanil and cycloguanil in human plasma by high-performance liquid chromatography

Edstein, Michael D.

doi:10.1016/s0378-4347(00)83641-5

Cited by 25 publications

(11 citation statements)

References 8 publications

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“…The half-life for the rapid phase corresponded with that calculated from plasma data (ti/, = 17.5 h) and is slightly slower than that of proguanil (t>/: = 14-17 h) [4]. The corre sponding excretion rate-time plot for chlorcycloguanil (rapid phase) has a tV l of 20 h ( fig.…”

Section: Discussionsupporting

confidence: 67%

Pharmacokinetics of Chlorproguanil in Man after a Single Oral Dose of Lapudrine®

Veenendaal¹,

Edstein²,

Kh³

1988

Chemotherapy

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The pharmacokinetic parameters of chlorproguanil (Lapudrine®) and its active metabolite, chlorcycloguanil, were determined in 6 healthy male volunteers after a single oral dose of 4 Lapudrine tablets (80 mg). The mean maximum plasma chlorproguanil concentration was 36.7 ± (SD)7.9 ng/ml and was reached at 3.8+1.3 h. The chlorproguanil elimination half-life was 17.5 ± 6.7 h and its plasma clearance was 1.28 ± 0.12 1/h/kg. The mean whole blood to plasma ratio was 3.1 at 4 h after dosing. Chlorcycloguanil could not be quantified in plasma and whole blood at the detection limit of 10 ng/ml using a high-performance liquid chromatographic method. An excretion rate-time plot from urine data shows a rapid (t_½ = 20 h) and a slow phase (t_½ = 51 h) in the elimination of chlorcycloguanil. Our findings suggest that the current prophylactic regimen of chlorproguanil hydrochloride (20 mg weekly) may not be optimal in preventing infections with chloroquine-resistant falciparum malaria.

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Section: Discussionsupporting

confidence: 67%

Pharmacokinetics of Chlorproguanil in Man after a Single Oral Dose of Lapudrine®

Veenendaal¹,

Edstein²,

Kh³

1988

Chemotherapy

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“…Concentrations of the metabolite 4-chlorophenylbiguanide in the present study were also approximately four times higher in whole blood compared with plasma. In contrast the active antimalarial metabolite cycloguanil was not concentrated in red (Maegraith et al, 1946;Ritschel et al, 1978), 12 (Taylor et al, 1984) and 17 (Edstein, 1986) h and a cycloguanil activity terminal half-life of 11 h derived from bioassay (Watkins et al, 1987). This supports prescription of the drug on a daily basis.…”

Section: Discussionmentioning

confidence: 90%

“…Recently several specific h.p.l.c. assay methods have been described (Moody et al, 1980;Edstein, 1986;Kelly & Fletcher, 1986) and some preliminary plasma drug concentration data have been reported, but these have been insufficient for adequate pharmacokinetic analysis. We have now refined the sensitivity and specificity of the earlier h.p.l.c.…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.

Wattanagoon

Taylor

Moody

et al. 1987

Brit J Clinical Pharma

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Hospital, Headington, Oxford OX3 9DU 1 Plasma and whole blood concentrations of proguanil and its two major metabolites cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) were measured by a sensitive h.p.l.c. technique in nine healthy adult male volunteers after a single oral dose of proguanil 200 mg.2 Proguanil was absorbed with a median time to peak plasma concentration of 3 h (range 2-4 h).3 Peak plasma concentrations of proguanil ranged between 150 and 220 (median 170) ng ml-' compared with 12 to 69 (median 41) ng ml-' for the active antimalarial metabolite CG, and 3 to 16 (median 11) ng ml-' for CPB. Peak (mean ± s.d.) plasma CG concentrations occurred 5.3 ± 0.9 h and peak CPB concentrations occurred 6.3 ± 1.4 h after oral administration of proguanil. 4 Whole blood concentrations of proguanil were approximately five times higher, and whole blood CPB concentrations were four times higher than corresponding plasma values, whereas plasma and whole blood concentrations of CG were similar. 5 A triexponential function was fitted to these data; mean (± s.d.) values for the AUC were 3046 ± 313 ng ml-' h for proguanil, 679 ± 372 ng ml-' h for CG and 257 ± 155 ng ml-1 h for CPB. 6 Plasma and whole blood concentrations of proguanil and its metabolites declined in parallel with terminal elimination half-lives estimated as 16.1 ± 2.9 h and 15.7 + 2.4 h, respectively. Mean residence times in plasma and whole blood were estimated as 21.2 ± 4.9 and 19.3 ± 2.4 h.

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“…Proguanil and cycloguanil concentrations in plasma, whole blood, erythrocytes and urine were measured by the HPLC method of Edstein [13] with minor modifications. Samples were chromato graphed on a Spherisorb phenyl reversed-phase col umn (15 cm x 4.6 mm inner diameter, 5 pm particle size).…”

Section: Methodsmentioning

confidence: 99%

Steady-State Kinetics of Proguanil and Its Active Metabolite, Cycloguanil, in Man

Edstein¹,

Veenendaal²,

Scott³

et al. 1988

Chemotherapy

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The pharmacokinetics of proguanil and its active metabolite, cycloguanil, were determined at steady-state in 6 healthy male volunteers after daily administration of 2 Paludrine® tablets (200 mg proguanil hydrochloride). A maximum plasma proguanil concentration of 130.3 ± 16.0 ng/ml (mean ± SD) was reached at 3.8 ± 1.3 h while a maximum cycloguanil concentration of 52.0 ± 15.2 ng/ml was obtained at 5.3 ± 1.0 h after dosing. The elimination half-lives of proguanil and cycloguanil were 14.5 ± 3.0 h and 11.7 ± 3.1 h, respectively. The plasma clearance of proguanil was 1.43 ± 0.33 1/h/kg and the apparent volume of distribution was 30.7 ± 12.3 1/kg. Renal clearance of proguanil (0.33 ± 0.19 1/h/kg) was about 23% of the plasma clearance and 35.6 ± 9.6% of the oral dose was recovered as proguanil and cycloguanil.

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Simultaneous measurement of proguanil and cycloguanil in human plasma by high-performance liquid chromatography

Cited by 25 publications

References 8 publications

Pharmacokinetics of Chlorproguanil in Man after a Single Oral Dose of Lapudrine®

Pharmacokinetics of Chlorproguanil in Man after a Single Oral Dose of Lapudrine®

Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.

Steady-State Kinetics of Proguanil and Its Active Metabolite, Cycloguanil, in Man

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