Determination of a potent urokinase-type plasminogen activator, UK-356,202, in plasma at pg/mL levels using column-switching HPLC and fluorescence detection.

A rapid, sensitive and selective method using column-switching HPLC with fluorescence detection has been developed for the determination of UK-356,202, a potent urokinase-type plasminogen activator, in human plasma. A structural isomer of UK-356,202 is used as an internal standard. The lower limit of quantification is 20 pg/mL and the method is linear over a 100-fold concentration range.

Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects.

Aims: Two studies were conducted to: (i) quantify the amount of drug-related radioactivity in blood, plasma, urine and faeces following a (14)C-labelled dose of maraviroc; and (ii) investigate the pharmacokinetics, safety and tolerability of intravenous (i.v.) maraviroc and determine the absolute bioavailability of oral maraviroc.

The use of 96-well Scintiplates to facilitate definitive metabolism studies for drug candidates.

Semi-quantitative analysis of the drug-related components in biological samples collected during definitive metabolism studies using radiolabelled drug candidates is commonly achieved by HPLC profiling, using either on-line radiochemical detection or off-line liquid scintillation counting (LSC) following collection of the HPLC eluent into vials. However, although the use of LSC with vials has high sensitivity, the approach is time-consuming, laborious and destructive, whilst on-line detection methods are inappropriate for samples with low-levels of radioactivity (commonly the case with plasma samples). The use of 96-well microtitre plates (Scintiplates) for fraction collection during HPLC profiling provides a sensitive, effective and efficient alternative method for the semi-quantitative analysis of radiolabelled components in biological samples.

Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil.

Aims: To characterize the absorption, metabolism and excretion of an oral and intravenous (IV) dose of radiolabelled [14C]-sildenafil citrate in healthy male subjects. Specific objectives were to measure the cumulative amount of drug-related radiolabelled material excreted in the urine and faeces to characterize urinary and faecal radioactivity as unchanged sildenafil or its metabolites, and to quantify blood and plasma total radioactivity and unchanged drug concentrations.

Methods: Six healthy male subjects between the ages of 45 and 58 years were enrolled in an open-label, parallel-group study; three subjects received the oral dose and three received the IV dose.