A dose finding study of prochlorperazine as an antiemetic for cancer chemotherapy

A Double-Blind Randomized Cross-Over Comparison of High-Dose Prochlorperazine with High-Dose Metoclopramide for Cisplatin-Induced Emesis

“…In addition, many prognostic factors have recently been reported to affect the emetic response to cisplatin, which include sex, concurrent drugs, perfor mance status and the age of the patients included [26]. As previously reported, higher than normal doses of prochlorperazine are well tolerated [20,27] and the results of this study emphasize this point. As reported by Carr et al [20] as well, drowsiness was the most frequent side effect experienced by our patients (table 3).…”

“…Olver et al [27] also did not record any severe dystonie reactions with high-dose prochlorperazine [27]. Hy potension, a known side effect at higher doses and rapid infusion rates of prochlorperazine, was not ex perienced by any of our patients.…”

A Double-Blind Randomized Cross-Over Comparison of High-Dose Prochlorperazine with High-Dose Metoclopramide for Cisplatin-Induced Emesis

“…In addition, many prognostic factors have recently been reported to affect the emetic response to cisplatin, which include sex, concurrent drugs, perfor mance status and the age of the patients included [26]. As previously reported, higher than normal doses of prochlorperazine are well tolerated [20,27] and the results of this study emphasize this point. As reported by Carr et al [20] as well, drowsiness was the most frequent side effect experienced by our patients (table 3).…”

“…Olver et al [27] also did not record any severe dystonie reactions with high-dose prochlorperazine [27]. Hy potension, a known side effect at higher doses and rapid infusion rates of prochlorperazine, was not ex perienced by any of our patients.…”

The Pharmacokinetics and Bioavailability of Prochlorperazine Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers

“…The good simultaneous fit of the same two‐compartment pharmacokinetic model to the venous plasma prochlorperazine concentration vs. time data after both aerosol and intravenous administration—without systematic deviations of the observed data from the calculated values and without model misspecification ()—suggests that the distribution pharmacokinetics of the drug is unaffected by the route of administration. In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others 5 , 5 , 5 …”

“…In this study, multiple peaks were detected in the plasma prochlorperazine concentration profiles, both after intravenous administration and after inhalational prochlorperazine administration. Others have noted a “somewhat erratic initial ‘distribution' phase” following a 20 min intravenous prochlorperazine infusion to patients, but they have not attempted to characterize it 12 . Multiple plasma concentration peaks after nonintravenous drug administration have been characterized by multiportion absorption models, including parallel first‐order absorption models and discontinuous first‐order absorption models 18 .…”

“…In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others. 4,5,12 The geometric mean bioavailability of prochlorperazine administered by inhalation to volunteers was 1.10 of the coated dose, despite in vitro evidence that the emitted dose was only 80% of the coated dose. At least one other study of pulmonary drug delivery found complete bioavailability of the nominal dose despite an in vitro estimate that bioavailability would be 50% of that dose, but it had no testable explanation for this observation.…”

A Double-Blind Randomized Cross-Over Comparison of High-Dose Prochlorperazine with High-Dose Metoclopramide for Cisplatin-Induced Emesis

“…In addition, many prognostic factors have recently been reported to affect the emetic response to cisplatin, which include sex, concurrent drugs, perfor mance status and the age of the patients included [26]. As previously reported, higher than normal doses of prochlorperazine are well tolerated [20,27] and the results of this study emphasize this point. As reported by Carr et al [20] as well, drowsiness was the most frequent side effect experienced by our patients (table 3).…”

“…Olver et al [27] also did not record any severe dystonie reactions with high-dose prochlorperazine [27]. Hy potension, a known side effect at higher doses and rapid infusion rates of prochlorperazine, was not ex perienced by any of our patients.…”

The Pharmacokinetics and Bioavailability of Prochlorperazine Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers

“…The good simultaneous fit of the same two‐compartment pharmacokinetic model to the venous plasma prochlorperazine concentration vs. time data after both aerosol and intravenous administration—without systematic deviations of the observed data from the calculated values and without model misspecification ()—suggests that the distribution pharmacokinetics of the drug is unaffected by the route of administration. In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others 5 , 5 , 5 …”

“…In this study, multiple peaks were detected in the plasma prochlorperazine concentration profiles, both after intravenous administration and after inhalational prochlorperazine administration. Others have noted a “somewhat erratic initial ‘distribution' phase” following a 20 min intravenous prochlorperazine infusion to patients, but they have not attempted to characterize it 12 . Multiple plasma concentration peaks after nonintravenous drug administration have been characterized by multiportion absorption models, including parallel first‐order absorption models and discontinuous first‐order absorption models 18 .…”

“…In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others. 4,5,12 The geometric mean bioavailability of prochlorperazine administered by inhalation to volunteers was 1.10 of the coated dose, despite in vitro evidence that the emitted dose was only 80% of the coated dose. At least one other study of pulmonary drug delivery found complete bioavailability of the nominal dose despite an in vitro estimate that bioavailability would be 50% of that dose, but it had no testable explanation for this observation.…”

A Double-Blind Randomized Cross-Over Comparison of High-Dose Prochlorperazine with High-Dose Metoclopramide for Cisplatin-Induced Emesis

“…In addition, many prognostic factors have recently been reported to affect the emetic response to cisplatin, which include sex, concurrent drugs, perfor mance status and the age of the patients included [26]. As previously reported, higher than normal doses of prochlorperazine are well tolerated [20,27] and the results of this study emphasize this point. As reported by Carr et al [20] as well, drowsiness was the most frequent side effect experienced by our patients (table 3).…”

“…Olver et al [27] also did not record any severe dystonie reactions with high-dose prochlorperazine [27]. Hy potension, a known side effect at higher doses and rapid infusion rates of prochlorperazine, was not ex perienced by any of our patients.…”

The Pharmacokinetics and Bioavailability of Prochlorperazine Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers

“…The good simultaneous fit of the same two‐compartment pharmacokinetic model to the venous plasma prochlorperazine concentration vs. time data after both aerosol and intravenous administration—without systematic deviations of the observed data from the calculated values and without model misspecification ()—suggests that the distribution pharmacokinetics of the drug is unaffected by the route of administration. In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others 5 , 5 , 5 …”

“…In this study, multiple peaks were detected in the plasma prochlorperazine concentration profiles, both after intravenous administration and after inhalational prochlorperazine administration. Others have noted a “somewhat erratic initial ‘distribution' phase” following a 20 min intravenous prochlorperazine infusion to patients, but they have not attempted to characterize it 12 . Multiple plasma concentration peaks after nonintravenous drug administration have been characterized by multiportion absorption models, including parallel first‐order absorption models and discontinuous first‐order absorption models 18 .…”

“…In this study, the volume of distribution and elimination clearance of prochlorperazine are very similar to those reported by others. 4,5,12 The geometric mean bioavailability of prochlorperazine administered by inhalation to volunteers was 1.10 of the coated dose, despite in vitro evidence that the emitted dose was only 80% of the coated dose. At least one other study of pulmonary drug delivery found complete bioavailability of the nominal dose despite an in vitro estimate that bioavailability would be 50% of that dose, but it had no testable explanation for this observation.…”