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Atrophic gastritis caused by chronic Helicobacter pylori (Hp) infection is related to the development of gastric cancer. Serum pepsinogen (PG) levels have been known as serological markers of atrophic gastritis. Individuals with serum PG I≤70 ng/mL and with a PG I/II ratio of≤3.0 have been thought to be at a higher risk for gastric cancer and were considered as “positive for the PG-method”. Recently, polymorphisms of interleukin-1 beta were reported to be associated with gastric cancer risks. Therefore, we examined the relationship between IL-1B polymorphisms and serum PGs in subjects who underwent a medical check-up in relation to Hp-infection. In the Hp-negative group, there were no subjects positive for the PG method. In the Hp-positive group, the incidence of IL-1B-511 T/T in the group positive for the PG method was significantly higher in comparison with that in the group negative for the PG method. Polymorphisms of IL-1B-511 appears useful for the selection of individuals who should undergo Hp-eradication therapy before progression of atrophic gastritis.

Effect of low-dose ranitidine on gastric pH after stimulation of gastric fluid secretion was evaluated using 4μg/kg of intramuscularly administered tetragastrin (TG) in 12 healthy male volunteers. The study was a randomized, placebo-controlled, four-way, cross-over trial. A wash-out period of 1-week was maintained between each treatment. Treatment administration was as follows: (1) 14.06 mg (hereafter 14mg) ranitidine, TG at t=1hr.(2) 28.13 mg (hereafter 28mg) ranitidine, TG at t=1hr.(3) 56.25mg (hereafter 56mg) ranitidine, TG at t=1hr.(4) Placebo, TG at t=1hr. Gastric pH was continuously monitored for 6 hours through a micro-pH-electrode in every subject. Gastric fluid acidity was measured at t=0, 1, 2, 3, 4 and 5 hr after ranitidine administration. Average gastric pH values for 6 hours were increased by ranitidine treatment from 2.08±0.48 (placebo) to 3.60±1.10 (14 mg, p

The urinary excretion of metabolites of bifemelane hydrochloride (BFM) was studied in both young and elderly volunteers. BFM (50mg) was administered orally after breakfast to young healthy subjects (n=8) and elderly subjects (n=15). Urine was collected separately 0-8 and 8-24hr after administration, and the concentrations of metabolites including a new identified metabolite, M-2 sulfate, were determined. The excretion rate of M-2 sulfate within 24hr after administration, which was 27.55±3.25% of the dose in young and 20.88±1.56% of the dose in elderly subjects, was larger then that of any other metabolites. The excretion rate of total metabolites in the young for 8hr post-administration was 54.11±2.94% of the dose, which was significantly higher (P

The effects of ranitidine, metoclopromide, and anisotropine methylbromide on the absorption of cefpodoxime proxetil (CS-807) were examined in two studies. Pharmacokinetic parameters of R-3763, an active metabolite of CS-807 by non-specific esterases in the intestinal wall, were calculated and compared.1) A single dose of ranitidine (150 mg) was administered orally to six healthy male subjects 1. 5 hr before the dose of CS-807 (100 mg). Intragastric pH was monitored through a micro-pH-electrode for 6.5 hr after ranitidine treatment (two-way crossover).2) Nine healthy volunteers were studied for the effect of metoclopromide (MCP) and anisotropine methylbromide (ATMB) (three-way crossover).Ranitidine treatment resulted in a significant decrease in the parameters: ka (from 0.957±0.052l/hr to 0.612±0.030l/hr; P

The pharmacokinetics of cefmetazole were investigated in 7 elderly patients (4 males, 3 females) and in 5 healthy volunteers (males). The drug was given in travenously at 10 mg/kg. The creatinine, clearance values of the elderly patients and healthy volunteers were 53.6 to 64.5 ml/min and 93.7 ml/min, respectively. The concentrations of cefmetazole in the serum and urine were determined by bioassay, and pharmacokinetic parameters were calculated on the basis of a two-compartment open model. The cumulative urinary excretion of cefmetazole at 8 hr after its injection was about 90% of the total dose in healthy volunteers, and about 60% of the dose in elderly patients. A negative correlation between age and the elimination rate constant (β), and a posltive correlation between age and the volume of distribution were observed. From these results, it was suggested that the decreased renal function reduced urinary excretion of cefmetazole in elderly patients, while the increased volume of distribution of cefmetazole, in particular, in bedridden elderly patients may be caused by age.

2 [4-(2-Thiazolyloxy) phenyl] propionic acid (156-S) is a new acidic nonsteroidalanti-inflammatory and analgesic agent. The pharmacokinetics of 156-S in elderlypatients were studied in comparison with those in healthy volunteers. The elderlypatients females, N=6, age: 84.7±2.1yr old, body weight: 29.7±2.0kg, serumconcentration of albumin: 3.3±0.1g/dl, creatinine clearance (CLcr: 61.3±8 .0ml/min ; all data are represented as mean±S. D.) were given 156-S (300mg) orally andblood and urine samples were taken after dosing. The same schedule applied to healthyvolunteers (males, N=6, 28.0±4.6yr old, 66.7±5. kg, 4.3±0.3g/dl, 91.1±14.0ml/min). The pharmacokinetic arameters of 156-S in both groups were calculated bythe one-compartment model. Although Cmax and Kab of 156-S in elderly patients were notdifferent from those in healthy volunteers, Tmax, AUC, t1/2 and Vd of 156-S in elderlypatients were shown to be significantly increased.More than 90% of the dose of 156-S was excreted in urine until 24 hr afteradministration in both groups. The value of CLr (M-I) (renal clearance of M-I, 156-Smajor metabolite) or CLr (total M) (renal clearance of total 156-S metabolites) obtained was bigger than that of CLcr in healthy volunteers, indicating that oxidativemetabolites of 156-S were excreted by glomerular filtration and renal tubular secretion.In elderly patients reduced CLr (M-I) and CLr (total M) were shown to be 40% ofthose in healthy volunteer and CLcr were about 60% . These data suggest that bothglomerular filtration and renal tubular secretion in elderly patients are reducedcompared to those in healthy volunteers.Hepatic clearance of 156-S in elderly patients, CLg (hepatic glucronidative clearanceof 156-S) and CLm (hepatic oxidative clearance of 156-S), were 30-40% of those inhealthy volunteers, indicating that hepatic metabolism of 156-S in elderly patient isreduced compared to those in healthy volunteers. Serum albumin binding ratios weresignificantly different between the two groups and serum concentration of albumin inelderly patients was much lower than in healthy volunteers. From these results, when wegive 156-S to elderly patients, we have to consider the adjustment of the dosing intervalrather than the dose of 156-S.

Malotilate (diisopropyl-1, 3-dithio1-2-ylidenemalonate) exists in two polymorphic forms, designated A and B. The transformation from A to B easily occurs at relatively low temperatures. Since different crystalline forms of a drug may influence its absorption and hence its therapeutic efficacy, two crystalline forms of malotilate (A and B) were assessed in 20 healthy male subjects using a two-way cross-over design. The concentration-time curve was shifted slightly to the right in the group that received the B form; however, there were no significant differences in the AUC, Cmax, and tmax between the two groups. Statistical evaluation of the data involved an analysis of variance for a cross-over design (ANOVA). This revealed significant differences for “Time Periods” and “Between Subjects, ” but not for “Group or Sequence” or “Drugs.” With 95% confidence, the confidence intervals of each parameter satisfied the criteria for AUC but not for Cmax and tmax. From the data obtained and taking into consideration their clinical use, we conclude that both the A and B forms of malotilate are bioequivalent.

The pharmacokinetics of tenoxicam (Ro 12-0068), a thienothiazine derivative with analgesic and anti-inflammatory properties, was studied with 5 healthy male volunteers, 5 elderly male patients, and 4 bedridden elderly female patients. After a single oral administration of 10 mg tenoxicam, the concentrations of tenoxicam in the venous blood and a metabolite of tenoxicam (5'-hydroxy-tenoxicam) in urine were determined at various times by HPLC.The pharmacokinetic parameters of tenoxicam were calculated by a one-compartment model. The respective Cmax, Tmax, Cl, T1/2, AUC, and Kel between the healthy volunteers and elderly patients were similar in level. The apparent Vd in the healthy volunteers and elderly male and female patients were 0.147, 0.192, and 0.273l/kg, respectively, and the apparent Vd in elderly patients was significantly larger than that in healthy volunteers (P