Quantification of perifosine, an alkylphosphocholine anti-tumour agent, in plasma by pneumatically assisted electrospray tandem mass spectrometry coupled with high-performance liquid chromatography

Knebel, Norbert; Grieb, Sally; Winkler, Marcus; Locher, Mathias; Vlis, E. van der; Verheij, Elwin

doi:10.1016/s0378-4347(98)00469-1

Cited by 18 publications

(16 citation statements)

References 15 publications

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“…For the Pediatric Indian and Adult Indian studies, a validated quantitative method was used with a lower limit of quantitation (LLOQ) of 5 ng/ml, based on a previously reported method for the structural analog perifosine (31). For the Adult European study, a previously reported validated quantitative method was used with an LLOQ of 4 ng/ml (16).…”

Section: Methodsmentioning

confidence: 99%

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

Dorlo

Huitema

Beijnen

et al. 2012

Antimicrob Agents Chemother

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bOnly anecdotal data are available on the pharmacokinetics (PK) of miltefosine in children suffering from visceral leishmaniasis (VL). While failure rates were higher in children with VL, steady-state concentrations appeared lower than those seen with adults. We hypothesized that the current linear dosage (in milligrams per kilogram of body weight) is too low for children and that a new dosing algorithm based on an appropriate body size model would result in an optimal exposure. A population PK analysis was performed on three historic pooled data sets, including Indian children, Indian adults, and European adults. Linear and allometric scaling of PK parameters by either body weight or fat-free mass (FFM) was evaluated for body size models. Based on the developed PK model, a dosing algorithm for miltefosine in children and adults was proposed and evaluated in silico. The population PK model employing allometric scaling fitted best to the pooled miltefosine data. Allometric scaling by FFM reduced between-subject variability, e.g., for drug clearance, from 49.6% to 32.1%. A new allometric miltefosine dosing algorithm was proposed. Exposure to miltefosine was lower in children than adults receiving 2.5 mg/kg/day: a C max of 18.8 g/ml was reached by 90% of adults and 66.7% of children. The allometric daily dose resulted in similar levels of exposure to miltefosine for adults and children. The use of a new allometric dosing algorithm for miltefosine in VL patients results in optimal exposure to miltefosine in both adults and children and might improve clinical outcome in children.V isceral leishmaniasis (VL) or kala-azar (Hindi for "black fever") has been classified as one of the world's "most neglected diseases" (62), and of all the parasitic diseases, it ranks third in terms of morbidity and mortality after only malaria and lymphatic filariasis (38). The World Health Organization (WHO) reported in 2004 that leishmaniasis is responsible for around 50,000 deaths and almost 2 million disability-adjusted life-years per year, approximately half of which can be attributed to children from lowincome countries (38, 60), but in reality the burden of leishmaniasis is probably much larger due to massive underreporting of both cases and deaths in the often remote areas where leishmaniasis is prevalent (47).Miltefosine (hexadecylphosphocholine; marketed by Paladin Laboratories Inc. as Impavido) is the newest addition to the small repertory of antileishmanial drugs and to date is the only drug that can be administered orally. It has achieved relatively high cure rates in the treatment of visceral (8, 26, 41, 52, 54), New World cutaneous (11,44,48,50,57), Old World cutaneous (30, 56) and even difficult-to-treat mucocutaneous (49, 51) leishmaniasis.During the development of miltefosine, two clinical trials were designed to investigate the efficacy and safety of miltefosine in children (Ͻ12 years of age) in which a total of 119 pediatric patients were enrolled, employing dosages linearly extrapolated from the daily adult dosage (in ...

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Section: Methodsmentioning

confidence: 99%

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

Dorlo

Huitema

Beijnen

et al. 2012

Antimicrob Agents Chemother

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“…Poor retention, severe peak tailing, and peak broadening of alkylphosphocholines using common reversed-phase columns has been previously reported [10][11][12][13]. Only slight peak tailing was observed on a normal-phase column for the analysis of perifosine, an alkylphosphocholine anticancer drug [12].…”

Section: Clr1401 (mentioning

confidence: 78%

“…The poor chromatography behavior of alkylphosphocholines was likely a result of interaction between the quaternary ammonium group of the phosphocholine molecules and stationary phases of common reversed-phase columns [10,12]. In the current study, reversed-phase columns were also evaluated and yielded poor chromatography during method development (data not shown).…”

Section: Lc-ms/ms Analysismentioning

confidence: 83%

“…The extraction of alkylphosphocholines from plasma samples using protein precipitation [10,11] and solid phase extraction [12,13] has been reported. For the present study, different extraction techniques, including protein precipitation and liquid-liquid extraction, were evaluated to improve extraction efficiency, reduce endogenous interference, and minimize the matrix effect of CLR1401.…”

Section: Clr1401 (mentioning

confidence: 99%

“…Only slight peak tailing was observed on a normal-phase column for the analysis of perifosine, an alkylphosphocholine anticancer drug [12]. To achieve good retention and minimize peak tailing of CLR1401, reversedphase columns and silica columns were evaluated.…”

Section: Clr1401 (mentioning

confidence: 99%

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Quantification of CLR1401, a novel alkylphosphocholine anticancer agent, in rat plasma by hydrophilic interaction liquid chromatography–tandem mass spectrometric detection

Jiang

Cannon

Banach

et al. 2010

Journal of Chromatography B

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Paclitaxel

2010

Analytical Methods for Therapeutic Drug Monitoring and Toxicology

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Quantification of perifosine, an alkylphosphocholine anti-tumour agent, in plasma by pneumatically assisted electrospray tandem mass spectrometry coupled with high-performance liquid chromatography

Cited by 18 publications

References 15 publications

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

Quantification of CLR1401, a novel alkylphosphocholine anticancer agent, in rat plasma by hydrophilic interaction liquid chromatography–tandem mass spectrometric detection

Paclitaxel

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