Bioavailability and cardiovascular safety of dexatrim® (phenylpropanolamine hydrochloride) from a controlledrelease caplet

Abstract

The bioavailability and pharmacokinetics of phenylpropanolamine hydrochloride (PPA HCl) from a Dexatrim controlled-release (CR) caplet and solution was studied. Each subject (n = 12) received either a 75 mg PPA HCl CR caplet once daily or a 25 mg PPA HCl solution given three times a day. All subjects received the medication for 4 consecutive days. On Day 1, the mean +/- SEM, AUC, tmax, and Cmax values were 1651 +/- 127 ng x h ml-1, 4.5 +/- 0.26 h and 143 +/- 13.5 ng ml-1, respectively, for the CR caplet and 1716 +/- 90.3 ng x h ml-1, 1.25 +/- 0.08 h and 126 +/- 5.8 ng ml-1 for the solution, respectively. At steady state (Day 4), the mean +/- SEM, AUC, tmax, and Cmax values were 1832 +/- 101 ng x h ml-1, 4.17 +/- 0.17 h and 151 +/- 6.5 ng ml-1, respectively, for the CR caplet and 2014 +/- 116 ng x h ml-1, 1.33 +/- 0.09 h and 143 +/- 8.7 ng ml-1, respectively, for the solution. The data from Day 1 were fitted to an oral one compartment model with a first order absorption rate constant, kA, first order elimination rate constant, k and lag time. The mean +/- SEM, kA, elimination half-life and lag time for PPA HCl from the CR caplet were 0.488 +/- 0.182 ng h ml-1, 5.84 +/- 1.66 h and 0.394 +/- 0.224 h, respectively. The mean +/- SEM, kA, elimination half-life and lag time for PPA HCl from the solution were 2.87 +/- 1.51 ng x h ml-1, 3.73 +/- 1.21 h, and 0.325 +/- 0.101 h, respectively. The smaller apparent kA and longer elimination half-life for PPA HCl from the CR caplet is due to the slow release of PPA HCl, thereby slowing its absorption producing sustained plasma drug concentrations. Blood pressures (supine and sitting) and heart rates measured at the time of blood sampling after the administration of the PPA HCl dosage forms demonstrated no clinically significant relationship between cardiovascular response and PPA HCl plasma concentration. These data demonstrate the bioavailability and pharmacokinetics of PPA HCl from a CR caplet and an immediate release solution.

Elimination of ephedrines in urine following multiple dosing: the consequences for athletes, in relation to doping control

“…The pharmacokinetic parameters for pseudoephedrine and phenylpropanolamine administered in liquid formulations such as solution or syrup, have been established [3,4]. Findlay and colleagues [5] have examined the plasma pharmacokinetic parameters or pseudoephedrine following administration of multiple, therapeutic doses.…”

Pharmacokinetics and Unexpected Safety Issues of LBM415, a Novel Oral Peptide Deformylase Inhibitor

“…Changes in absorption rate are common when a drug is coadministered with food, and it is well known that meals delay gastric emptying 21 . Previous reports have shown that LBM415 is completely absorbed from the gastrointestinal tract, suggesting that it has high permeability through the GI tract.…”

Treatment of urethral sphincter mechanism incompetence in 11 bitches with a sustainedrelease formulation of phenylpropanolamine hydrochloride

“…It has been shown that the peak plasma concentrations of phenylpropanolamine are not significantly different after the oral administration of equal doses of either immediate‐ or sustained‐release formulations (Hussain and others 1987, Lasagna 1988, Shargel and others 1990). After a single dose of an immediate‐release aqueous solution there is a rapid increase in the plasma concentration followed by a fairly rapid decline (Fig 1).…”

“…In contrast, sustained‐release preparations deliver the drug more slowly and the peak plasma concentration is reached more slowly (Lönnerholm and others 1984, Hussain and others 1987, Lasagna 1988, Shargel and others 1990). There is an initial release of drug that produces a plasma peak within the first few hours of the oral administration, and this is followed by a second slower absorption phase which continues over 16 hours and maintains the plasma concentration at a more constant level (Hussain and others 1987) (Fig 2).…”