A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly

Figures & data

Table 1 Common causes of constipation in elderly patients

Gastrointestinal disorders	Irritable bowel syndrome
	Anorectal disorders (ie, hemorrhoids, anal fissures)
	Diverticulitis
	Hernias
	Intestinal volvulus
	Tumors
	Upper gastrointestinal tract disorders
Metabolic disorders	Diabetes mellitus
	Chronic kidney disease
	Hypothyroidism
	Hyperparathyroidism
	Hypercalcemia
	Panhypopituitarism
Neurogenic disorders	Cerebrovascular accidents
	Parkinson’s disease
	Spinal cord injury (ie, spinal canal stenosis)
	Tumors of the central nervous system
	Trauma to the brain or the medulla
Psychogenic causes	Voluntarily ignore or postpone defecation
	Psychiatric disease
Medications	Nonsteroidal anti-inflammatory agents
	Opiates
	Calcium channel blockers
	Diuretics (nonpotassium sparing)
	Iron supplements
	Antihistamine
	Anticholinergics
	Tricyclic antidepressants
	Antipsychotics
	Antacids containing calcium carbonate or aluminum hydroxide

Figure 1 Summary of the mechanism of action of lubiprostone.

Notes: Chloride channels-2, present in the apical membrane of the intestine, are activated, resulting in increased secretion of chloride-rich intestinal fluid. Other channels secondarily act to maintain cellular homeostasis.
Abbreviations: LUB, lubiprostone; ClC₂, chloride channels-2.

Table 2 Summary of clinical trials of lubiprostone in adult populations with chronic constipation

Author	Patients	Description	Results
Johanson et al^Citation34	N = 129 Age 18–75 >84% women	3-week dose ranging study (24 mcg/d, 48 mcg/d and 72 mcg/d doses)	Dose-dependent improvement SBM on day 1, SBMs/week, stool consistency, straining and bloating in lubiprostone arms, accompanied by incremental incidence of adverse events (nausea, headache, and diarrhea).
Johanson et al^Citation2	N = 242 Age 22–80 90% women	4-week single dose study (24 mcg bid)	Lubiprostone better than placebo on SBM on day 1, SBMs/week after week 1, stool consistency, straining, abdominal bloating, abdominal discomfort, and constipation severity. Nausea more frequent in lubiprostone group (31.7% vs 3.3% in placebo group).
Barish et al^Citation34	N = 237 88.2% women	4-week single dose study (24 mcg bid)	Lubiprostone better than placebo on SBM on day 1 and SBMs/week after week 1. Stool consistency, straining, and constipation severity. No significant differences in abdominal bloating and discomfort.
Lembo et al^Citation36	N = 248 Mean age 51 ± 14 83.9% women	48-week open-label, single dose study (24 mcg bid) One subgroup enrolled after a placebo-controlled withdrawal phase	Significant reduction from baseline, in constipation severity, abdominal bloating, and abdominal discomfort.

Abbreviations: bid, twice daily; SBM, spontaneous bowel movement.

Table 3 Summary of clinical trials of lubiprostone in adult populations with IBS and predominant constipation

Author	Patients	Description	Results
Drossman et al^Citation37	N = 1171 Age 18–85 92% women	Two 12-week Single dose (8 mcg bid) trials	Higher rate of overall responders (subjective rate of relief of IBS symptoms): in lubiprostone group (17.9%) than placebo (10.1%), maintained throughout the study. Improvement in abdominal discomfort/pain, bloating, constipation severity, stool consistency, and straining (P < 0.001). Trends in improvement in IBS-QOL measures.
Chey et al^Citation38	N = 520 Age 21–82 93% women	36-week Single dose (8 mcg bid) open-label trials extension of placebo-controlled studies	Overall subjective rate of relief was 16% after 1 month, 23%–39% after 2–5 months, 37%–44% after 10–13 months of lubiprostone treatment. Increase in SBMs/week after the first month of treatment, maintained at approximately 5 SBMs/week throughout the treatment period, with improvement in abdominal discomfort/pain, abdominal bloating, and stool consistency after the first month and throughout the study (P < 0.001). Most common adverse events were nausea and diarrhea (both 11%).

Abbreviations: IBS, irritable bowel syndrome; bid, twice daily; QOL, quality of life; SBM, spontaneous bowel movement.

Table 4 Summary of clinical trials of lubiprostone in elderly adults

Author	Patients	Description	Results
Ueno et al^Citation39	N = 57 Age ≥ 65	Subanalysis of 3 pooled placebo-controlled single dose (24 mcg bid) clinical trials of 3–4 weeks duration	Significant improvement in lubiprostone group, in weeks 1, 3, and 4, of SBMs rates stool consistency, and bowel straining rates. Lesser adverse events in the lubiprostone group.
Ueno et al^Citation40	N = 878 (N = 163, age ≥ 65, N = 715 age 18–64)	Subanalysis of 3 pooled 48-week single dose (24 mcg bid) placebo-controlled trials	Significant improvement, in elderly and nonelderly groups, of constipation severity, abdominal bloating, and discomfort. Incidence of nausea: 17.8% in elderly vs 29.4% in nonelderly patients.

Abbreviations: bid, twice daily; SBM, spontaneous bowel movement.

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