Use of automatic computerised pump to maintain constant intragastric pH.

Abstract

We used continuous variable rate infusions of famotidine in eight normal volunteers under fasting conditions to raise intragastric pH to 5-0. An intragastric glass electrode continuously monitored acidity and this information was automatically computed to regulate an intravenous infusion system (Gastrojet). The computer was programmed to aim for pH 6*0, increasing and lowering infusion rates accordingly. Two regimens were compared with placebo (10 mg bolus followed by infusion or infusion of famotidine alone). Volunteers were admitted to an investigation ward and each study was preceded by a standard normal meal. Hydration was maintained with intravenous fluids. During placebo treatment the median pH was 1-5 and the pH was <5-0 for 98% of the time. All volunteers responded to famotidine but dosage requirements varied (range 41 mg to 126 mg). The median pH rose to 6*5 when infusions of famotidine followed boluses and to 6-6 when infusions alone were used -the pH was <5-0 for 20% (Ingold M440, Switzerland). The pH recording system has previously been described and validated.' A target pH is programmed and infusion rates are adjusted upwards until this value is reached. Rates are then decreased at 28 minute intervals while pH remains at or above target, but are increased after four minutes if the pH falls below target. A mark is recorded in the machines memory every time the rate is increased or decreased. Preliminary studies with the equipment had suggested that a target pH one unit higher than that actually expected should be programmed in order to limit fluctuations around the target value itself. A full validation study has been published elsewhere.6 Thus, a target of 6-0 was chosen for these studies. Famotidine, 40 ml (4 mg/ml), or placebo (normal saline) was loaded into plastic infusion bags which fit into the machine. The infusion bags were weighed before and after each study day to check on total infusion volumes. VOLUNTEERSEight healthy students (five men) participated in the study. They had normal biochemical profiles and haematology before entry and none required regular medication of any sort. The mean age was 22 years (range 20-25 years), mean weight was 72 kg (59-93 kg), and two were smokers. Informed consent was given and the study approved by the Central Birmingham Health Authority ethics committee. PROCEDURESVolunteers attended the investigation unit at 12 30 and a standard lunch was supplied (soup and roll, lasagne and ratatouille, chocolate mousse, coffee and mint chocolates: JS Sainsbury). The menu, quantity, and time of lunch were the same on every study day. Cigarette smoking and alcohol were not allowed.

Development of a Canine Model to Enable the Preclinical Assessment of Ph-dependent Absorption of Test Compounds

“…Gastric pH in humans has been evaluated using a variety of methodologies, including orogastric or nasogastric intubation and aspiration, direct measurement via a pH probe in the stomach, and radiotelemetry (e.g., Heidelberg capsule). Regardless of the method used, fasting gastric pH in humans has been reported to be less than 3 18–21. This has not been consistently observed in the dog.…”

Identical 24-hour Intragastric pH Response to Low Continuous Infusion Doses of Famotidine in Active Gastric Ulcer Patients.

“…A famotidine concentration of about 13 ng/ml has been considered to be the IC50. (15) Because in the elderly the half-life of famotidine is prolonged (ll), the mean famotidine concentrations in the 40mg/day group were as high as those generated by much higher doses administered to younger subjects,this could in itself explain the constant gastric pH response (7). In order to test the effect of much lower steady-state plasma concentrations on gastric acidity, slightly younger subjects were purposely included in group B.…”

“…All the above-mentioned reasons could explain why most 24h intragastric pH controlled reports up to the present recommend high doses of antisecretory intravenous (i.v.) infusions (5)(6)(7)(8)(9)(10).…”

“…dosage of H2-blockers presently used (6)(7)(8)(9)(10) and little attention has been paid to the effect of low doses. To establish a therapeutic plasma concentration and a dosage guideline, here the effect of 20 or 40mg/day famotidine on 24-h intragastric pH in active gastric body ulcer patients was analyzed.…”

Individual and group dose‐responses to intravenous omeprazole in the first 24 h: pH‐feedback‐controlled and fixed‐dose infusions.

“…The pH electrodes were connected to the microprocessor-controlled feedback infusion unit (Gastro-jet®, Medical Instruments Corp., Solothurn, Switzerland), comprised of a 24 h solid-state datalogger, which registers 5 s pH medians, and the infusion pump. The unit has been validated previously [13][14][15][16]. Briefly, the pump has 11 freely programmable infusion rates, between which the processor chooses to maintain the intragastric pH above a pre-determined target.…”