Bioavailability and cardiovascular safety of dexatrim® (phenylpropanolamine hydrochloride) from a controlledrelease caplet
✍ Scribed by Leon Shargel; Harold I. Silverman; Peri Cohen; Jerry Brisson; Susana Dennis
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 657 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0142-2782
No coin nor oath required. For personal study only.
✦ Synopsis
The bioavailability and pharmacokinetics of phenylpropanolamine hydrochloride (PPA HC1) from a DexatrimO controlled-release (CR) caplet and solution was studied. Each subject (n = 12) received either a 75mg PPA HCI CR caplet once daily or a 25 mg PPA HCI solution given three times a day. All subjects received the medication for 4 consecutive days. On Day 1, the mean f SEM, AUC, t,,,, and C, , , values were 1651 f 127ng x hml-I, 4.5 f 0.26h and 143 f 13.5ngml-', respectively, for the CR caplet and 1716 f 90.3ng x hml-', 1.25 f 0.08 hand 126 f 5.8ngml-' for the solution, respectively. At steady state (Day 4), the mean f SEM, AUC, t, , , , and C,,, values were 1832 f 101 ng x hml-I, 4.17 f 0.17h and 151 f 6.5ngml-I, respectively, for the CRcaplet and2014 f 116ng x hml-', 1.33 f 0.09hand 143 f 8.7ngml-', 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 f SEM, k,, elimination half-life and lag time for PPA HCl from the CR caplet were 0.488 f 0.182 ng h ml-', 5.84 f 1.66 h and 0.394 f 0.224 h, respectively. The mean f SEM, k,, elimination half-life and lag time for PPA HCI from the solution were 2.87 f 1.51 ng x hml-I, 3.73 f 1.21 h, and 0.325 f 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 HC1 dosage forms demonstrated no clinically significant relationship between cardiovascular response and PPA HCl plasma concentration. These data demonstrate the bioavailability and pharmacokinetics of PPA HCI from a CR caplet and an immediate release solution.