Repeat-dose steady-state pharmacokinetic evaluation of once-daily hydromorphone extended-release (OROS^® hydromorphone ER) in patients with chronic pain

Figures & data

Figure 1 Study design.

Abbreviation: HM ER, hydromorphone extended-release.

Figure 2 Patient disposition.

Table 1 Baseline demographics and characteristics

Characteristic	Patients (N = 22)
Sex, n (%)
Female	18 (81.8)
Male	4 (18.2)
Age, y, mean (range)	51.4 (25–81)
Weight, kg, mean (range)	76.2 (45–128)
Height, cm, mean (range)	166.9 (150–185)
Race, n (%)
White	20 (90.9)
Asian	1 (4.5)
Other	1 (4.5)
Pain type, n (%)
Musculoskeletal	19 (86.4)
Neuropathic	3 (13.6)
Pain intensity scorea
Mean (SD)	5.5 (2.1)
Median (min, max)	6.0 (2.0, 10.0)

Notes:

a Baseline was 0 hours at Visit 5; n = 17. Pain intensity was based on an 11-point scale (0 = no pain and 10 = pain as bad as you could imagine).

Abbreviation: SD, standard deviation.

Table 2 Concomitant medication use

Medication type	Patients (N = 22) n (%)	Medication (patients, n)a
Hormone therapy	15 (68.2)	Levothyroxine (4), estradiol (3), calcitonin (2), conjugated estrogens and medroxyprogesterone (1), esterified estrogens and methyltestosterone (1), estradiol valerate (1), estrogen (1), fluoxymesterone (1), levonorgestrel/ethinyl estradiol (1)
Antidepressant	10 (45.5)	Amitriptyline (3), bupropion (3), venlafaxine (2), paroxetine (1), sertraline (1)
Cardiovascular medication	10 (45.5)	Atenolol (1), benazepril (1), doxazosin (1), fosinopril (1), lisinopril (1), nifedipine (1), nitroglycerin (1), ramipril (1), simvastatin (1), verapamil (1)
Vitamin/other	9 (40.9)	Calcium carbonate (2), folic acid (2), glucosamine (2), chondroitin (1), glycerin (1), multiple vitamin (1)
Antihistamine	8 (36.4)	Promethazine (3), diphenhydramine (1), fexofenadine (1), hydroxyzine (1), loratadine (1), oxymetazoline (1)
Gastrointestinal/ gastroesophageal medication	8 (36.4)	Omeprazole (4), ranitidine (2), bismuth subsalicylate (1), cisapride (1)
Anticonvulsant/antispasmodic medication	4 (18.2)	Gabapentin (3), oxybutynin (1)
Antimetabolite	4 (18.2)	Methotrexate (4)
Muscle relaxant	4 (18.2)	Cyclobenzaprine (3), carisoprodol (1)
Respiratory medication	4 (18.2)	Cromolyn sodium (1), nedocromil (1), salmeterol (1), triamcinolone acetonide (1)
Steroid	4 (18.2)	Methylprednisolone (3), mometasone (1)
Anti-anxiety medication	3 (13.6)	Diazepam (3)
Benzodiazepine	3 (13.6)	Temazepam (2), lorazepam (1)
Diuretic	3 (13.6)	Dyazide (1), furosemide (1), torsemide (1)

Notes: In addition, alendronate, warfarin, cephalosporin (cephalexin), valacyclovir, and glyburide were each taken by one patient.

a More than one drug could be taken by one patient. Medications for pain and for constipation prophylaxis treatment were excluded.

Figure 3 Distribution of OROS^® hydromorphone extended-release (ER) doses at the start and end of the titration phase.

Figure 4 Mean (standard deviation) dose-normalized (to 16 mg dose) hydromorphone plasma concentration–time profile following the administration of OROS^® hydromorphone extended-release (n = 17).

Figure 5 Relationship between hydromorphone area under the concentration–time curve from 0–24 hours (AUC_0–24) and dose of OROS^® hydromorphone extended-release (ER).

Figure 6 Percentage of patients with plasma concentrations ≥ 50% maximum plasma concentration at each time point after dosing with OROS^® hydromorphone extended-release (n = 14).

Figure 7 Mean (standard error of the mean) pain intensity difference (PID) scores over 24 hours at Visit 5 (n = 17).

Notes: Assessments made using item 6 on the Brief Pain Inventory Short Form, “pain right now” (11-point scale; 0 = no pain and 10 = pain as bad as you could imagine). PID indicates difference from baseline for pain intensity score; small or negative values indicate pain relief is not being achieved, whereas large positive values indicate pain relief is being achieved. Inset: Overlay of mean PID scores over 24 hours with mean dose-normalized (to 16 mg dose) hydromorphone plasma concentration–time profile following the administration of OROS^® hydromorphone ER (n = 17). *P < 0.05; ^†P ≤ 0.0005; ^‡P < 0.004; ^§P < 0.002.

Table 3 Adverse events (AEs) reported by ≥5% of patients, by relationship to study drug

AE, n (%)	Patients (N = 22)	Relationship to OROS^® hydromorphone ER
		Unrelated	Unlikely	Possible	Probable
Constipation	7 (31.8)	–	2 (9.1)	4 (18.2)	1 (4.5)
Headache	5 (22.7)	1 (4.5)	4 (18.2)	–	–
Vomiting	3 (13.6)	1 (4.5)	–	2 (9.1)	–
Dry mouth	2 (9.1)	–	2 (9.1)	–	–
Injury, accidental	2 (9.1)	2 (9.1)	–	–	–
Nausea	2 (9.1)	1 (4.5)	–	1 (4.5)	–
Rash	2 (9.1)	1 (4.5)	–	1 (4.5)	–

Abbreviation: ER, extended-release.