Related Experiment Video
Updated: Apr 3, 2026

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone
Krishna Devarakonda1, Kenneth Kostenbader2, Michael J Giuliani3
1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
Objective:
This study aimed to compare the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) and IR HB/APAP.
Setting:
The study was conducted in a contract research center.
Participants:
The study included healthy adults.
Interventions:
In a three-way crossover study, Study 1, participants received the following treatments: (A1) a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h); (B1) a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1) a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6), followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2) an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2) three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h.
Main Outcome Measures:
PK values were compared, and adverse events were assessed.
Results:
Single-dose and steady-state area under the concentration-time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (C max) at steady state were also similar, but single-dose C max for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%-125%). Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median time to C max was longer for IR/ER HB/APAP versus IR HB/APAP (P,0.05). Adverse events were similar across treatments.
Conclusion:
PK outcomes and tolerability were similar for IR/ER HB/APAP and IR HB/APAP.
More Related Videos
Related Concept Videos
Modified-Release Drug Delivery Systems: Drug Release Characteristics
Drug Delivery Systems: Different Types
Bioavailability Study Design: Single Versus Multiple Dose Studies
Drug Accumulation During Multiple Dosing: Repetitive IV Injections
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Modified-Release Drug Delivery Systems: Bioavailability

