The rationale for this study is to investigate the absorption, metabolism and excretion of \[14C\]PF 02341066 and characterize plasma, fecal and urinary radioactivity, and identify any metabolites, if possible, of \[14C\]PF 02341066 in humans.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
oral suspension, single 250 mg dose of PF 02341066 containing approximately 100 µCi of \[14C\]PF 02341066
Pfizer Investigational Site
New Haven, Connecticut, United States
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours (hrs), 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast)
Area under the concentration time-curve from zero to the last measured plasma concentration (AUClast).
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Plasma Decay Half Life (t1/2)
Plasma Decay half-life is the time measured for the concentration to decrease by one half.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Apparent Oral Clearance (CL/F) of Plasma PF-02341066
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Apparent Volume of Distribution (V/F) in Plasma
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Renal Clearance (CLr) of PF-02341066
CLr is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to Infinite Time (Ae)
Ae = concentration of unchanged drug excreted in the urine multiplied by volume of unchanged drug excreted in urine.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Total Amount of Unchanged Drug Excreted in the Urine Expressed as Percent of Dose From Time Zero to Infinite Time [Ae(%)]
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Maximum Observed Concentration in Plasma Radioactivity (Cmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity Concentration (AUClast)
Area under the concentration time-curve from zero to the last measured plasma concentration. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Plasma Radioactivity Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in plasma. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Decay Half Life (t1/2) of Radioactivity in Plasma
Plasma decay half-life is the time measured for the plasma radioactivity concentration to decrease by one half. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Apparent Oral Clearance (CL/F) of Plasma Radioactivity
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Apparent Volume of Distribution (V/F) in Plasma Radioactivity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood
Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Radioactivity in Whole Blood
Area under the concentration time-curve from zero to the last measured concentration (AUClast) in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Radioactivity in Whole Blood
Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Decay Half-life (t1/2) of Radioactivity in Whole Blood
Decay half life (t1/2) is the time measured for the concentration to decrease by one half in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Apparent Oral Clearance of Radioactivity From Whole Blood (CL/F)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Apparent Volume of Distribution of Radioactivity in Whole Blood (V/F)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Total [14C] Data in Urine
Cumulative amount excreted in urine at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Total [14C] Data in Feces
Cumulative amount excreted in feces at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose
Overall Cumulative Percent Recovery of Radioactivity
Overall cumulative percent of radioactive dose recovered in urine, feces and toilet tissue at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: Pre-dose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose for urine and Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose for feces
Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma
Identification was done by Radio-High Performance liquid chromatography (HPLC) chromatogram. Relative abundance (profiling) of metabolites in chromatogram were determined by dividing sum of radioactive content of fractions contributing to particular peak by sum of radioactive content of all fractions constructing the radio chromatogram. Metabolites accounting for an average of greater than or equal to (\>=) 10% of total recoverable radioactivity in plasma were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces
In feces, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose
Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine
In urine, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose