Histamine2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing

Table 1 Intragastric pH studies demonstrating histamine₂-receptor antagonists¹ tachyphylaxis

Ref.	Design	Treatment regimen	Dosing duration	n	Days pH recorded	Tachyphylaxis observed
Wilder-Smith et al[38], 1990	OL	Famotidine 40 mg QD	28 d	14	1, 14, 28	Day 14
	R, PC, DB, crossover	Ranitidine 300 mg QID	7 d	10	1, 7, 28	Day 7
		Ranitidine 300 mg QHS	21 d
	R, PC, DB, crossover	Ranitidine 300 mg TID	14 d	14	1, 14	Day 14
		Ranitidine 300 mg QHS				Day 14
Smith et al[39], 1990	R, PC, crossover	Famotidine 40 mg QD	28 d	13	0, 1, 14, 28	Day 14
	R, PC, crossover	Ranitidine 300 mg QID	7 d	13	1, 8	Day 8
		Ranitidine 300 mg QHS	21 d			Day 8
Nwokolo et al[24], 1990	R, OL	Cimetidine 800 mg QD	29 d	48	0, 1, 15, 29	Day 15
		Nizatidine 300 mg QD				Day 15
		Famotidine 40 mg QD				Day 15
		Ranitidine 150 mg BID				Day 15
		Ranitidine 150 mg QD				Day 15
		Ranitidine 300 mg QD
Nwokolo et al[40], 1991	R, DB, PC	Ranitidine 150 mg QHS	5 mo	17	1, 29, 57, 85, 113, 141	Day 29
		Ranitidine 150 mg prn				Day 29
Wilder-Smith et al[23], 1992	R, PC, blinded, crossover	Ranitidine IV 0.25 mg/kg per hour	6 d	10	1, 6	Day 6
		Ranitidine IV by pH-feedback, up to 800 mg/24 h				Day 6
		Ranitidine 300 mg PO QID				Day 6
Merki et al[31], 1993	R, PC, crossover	Ranitidine IV ≤ 600 mg/24 h, pre/post 300 mg QD for 9 d	9 d	11	1, 9	Day 9
Merki et al[30], 1994	R, DB, crossover	Ranitidine IV, ≤ 576 mg/24 h	3 d	12	1, 3	Day 3
		Omeprazole IV, ≤ 288 mg/24 h				Not observed
Hurlimann et al[22], 1994	R, DB, parallel	Ranitidine 150 mg QID	14 d	28	1, 2, 7, 14	Day 2
		Omeprazole 40 mg QD				Not observed
Lachman et al[41], 2000	OL	Ranitidine 150 mg QID	5 d	28	1, 5	Day 5
Komazawa et al[20], 2003	R, crossover	Ranitidine 150 mg BID	14 d	7	1, 14	Day 14
		Famotidine 150 mg BID				Day 14
Hsu et al[18], 2004	R, OL	Cimetidine IV 1200 mg/24 h	5 d	80	1, 2, 3, 4, 5	Day 2
		Ranitidine IV 200 mg/24 h				Day 2
		Omeprazole IV 40 mg BID				Not observed
Miner et al[14], 2006	R, PC, crossover	Famotidine 10 mg BID	14 d	31	1, 3, 7, 14	Day 3
		Famotidine 20 mg QD				Day 3
		Omeprazole 20 mg QD				Not observed
Shimatani et al[25], 2007	R, OL, crossover	Famotidine 20 mg BID	15 d	8	1, 8, 15 1, 8, 15	Day 8
		Omeprazole 10 mg QD				Not observed
Fändriks et al[16], 2007	R, crossover	Famotidine 10 mg	8 d	8	1, 8	Day 8
		Omeprazole 20 mg				Not observed
Ono et al[15], 2008	R, crossover	Ranitidine 150 mg BID	10 d	7	-1, 1-7, 11-12 (no dose 8-10)	Day 2
		Rabeprazole 20 mg QD				Not observed

¹Includes only histamine₂-receptor antagonists marketed in the United States. All doses were administered orally unless specified otherwise. BID: Twice daily; HS: Bedtime; IV: Ntravenous; OL: Open-label; PC: Placebo-controlled; PRN: As needed; QD: Daily; QID: Four times daily; QHS: Every bedtime; R: Randomized.