Morphine sulfate hydrate/Oxycodone Hydrochloride Hydrate

Compare the efficacy and tolerability of the dual-opioid, Q8003(®) (morphine/oxycodone combination) 12 mg/8 mg to morphine 12 mg or oxycodone 8 mg in subjects following bunionectomy surgery.

This was a randomized, double-blind study.

Hospitalized patients.

Healthy men or women aged ≥18 years with moderate or severe pain (score ≥2 on a 4-point Likert scale) and ≥4 on the 11-point numerical pain rating scale following surgery.

Study medication was initiated after surgery and was given for 48 hours.

The primary efficacy variable was mean sum of the pain intensity difference (SPID) scores from the postsurgical baseline.

Five hundred twenty-two subjects were randomized; 31 (5.9%) discontinued, including 19 (3.6%) for adverse events. The mean total morphine equivalent dose (MED) was 182.7 mg from Q8003 12 mg/8 mg, 92.4 mg for morphine 12 mg, and 92.1 mg for oxycodone 8 mg. SPID from baseline over 24 hours and SPID from baseline over 48 hours were significantly (P < 0.02) higher for Q8003 12 mg/8 mg vs morphine 12 mg or oxycodone 8 mg. Significantly (P < 0.015) fewer subjects in the Q8003 group required ibuprofen rescue medication, used lower doses of rescue medication, and had a longer median time to first use of rescue medication. Oxygen desaturation <90% occurred in 5.3% with Q8003, 2.8% with morphine 12 mg, and 2.3% with oxycodone 8 mg, and the cumulative median dose at first desaturation was twofold greater with Q8003.

Q8003 provided superior efficacy to its individual components at twice the MED with only a modest increase in the incidence of adverse events.

InYersinia pestis,Y. pseudotuberculosis, andY. enterocolitica, phenotypic expression of virulence plasmid (pYV: 70-kb)-associated genetic determinants may include low-calcium response (Lcr, pinpoint colony, size = 0.36 mm), colony morphology (size = 1.13 mm), crystal violet (CV) binding (dark-violet colony), Congo Red (CR) uptake (red pinpoint colony, size = 0.36 mm), autoagglutination (AA = cells agglutinate), and hydrophobicity (HP = clumping of cells).Y. pseudotuberculosisis chromosomally closely related toY. pestis;whereas,Y. enterocoliticais chromosomally more distantly related toY. pestisandY. pseudotuberculosis. All three species demonstrate Lcr, CV binding, and CR uptake. The colony morphology/size, AA, and HP characteristics are expressed in bothY. pseudotuberculosisandY. enterocoliticabut not inY. pestis. Congo red uptake inY. pestiswas demonstrated only on calcium-deficient CR magnesium oxalate tryptic soy agar (CR-MOX), whereas this phenotype was expressed on both CR-MOX and low-calcium agarose media inY. pseudotuberculosisandY. enterocolitica. These phenotypes were detectable at 37°C within 24 h inY. enterocoliticaandY. pseudotuberculosisbut did not appear until 48 h inY. pestisdue to its slower growth rate at 37°C. The pYV is unstable (i.e., easily lost under a variety of culture conditions) in all three species but is more unstable inY. pestis. The specific CR uptake byY. pestisin CR-MOX and the delayed time interval to express Lcr and CR uptake provide a means to differentiateY. pestisfromY. enterocoliticaandY. pseudotuberculosis. These differences in pYV expression inY. pestiscan be used for its isolation and detection in food.