Biomedical subjects

G S Hughes

Publications and source records attributed to G S Hughes.

At least 19 recordsLinked to original sources

PubMed1995

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution.

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL-1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high-fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24 h period, and urine was collected for 48 h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability.

Administration, Oral↗

PubMed1995

Hemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans.

OBJECTIVE: The objective of this study was to evaluate the exercise capacity of subjects given an autologous transfusion or a polymerized bovine hemoglobin solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin-based oxygen carrier (HBOC-201). METHODS: Six normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery catheter was inserted in each subject before serial cardiac output and pulmonary function tests and phlebotomy of 15% blood volume (750 ml plus another 250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin). This was followed by isovolemic hemodilution with Ringer's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity) were done before phlebotomy and at approximately 45 minutes after the autologous transfusion or HBOC-201 infusion. RESULTS: Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201 (which paralleled plasma HBOC-201 levels) than during autologous transfusion periods. Oxygen use (uptake) and carbon dioxide production at rest were greater during the HBOC-201 infusion than during the autologous transfusion period. The half-life of HBOC-201 was about 23 hours. CONCLUSIONS: Exercise capacity and diffusion capacity were similar after HBOC-201 and autologous transfusion. HBOC-201 resulted in greater oxygen (or uptake) and carbon dioxide production and lower lactate levels compared with autologous transfusion. Under the conditions of the study, the physiologic effects of 1 gm bovine hemoglobin of HBOC-201 were similar to 3 gm human hemoglobin from autologous transfusion.

Adult↗

PubMed1995

Lifibrol: a novel lipid-lowering drug for the therapy of hypercholesterolemia. Lifibrol Study Group.

OBJECTIVE: To determine the effects of lifibrol on serum lipids in adult patients with primary hypercholesterolemia. METHODS: These were two double-blind, randomized placebo-controlled studies. Each patient in each study had an 8-week dietary lead-in period on the American Heart Association Step I diet before administration of lifibrol or placebo. The first study consisted of active dosing of 4 weeks, and the second study had 12 weeks of active dosing. The setting for the study involved outpatients in private or university hospitals in the United States. All patients had primary hypercholesterolemia with low-density lipoprotein (LDL) cholesterol levels of > 160 mg/dl after the dietary lead-in period. There were 155 patients in the 4-week study and 336 patients in the 12-week study. In the first study, patients were randomly assigned to receive either 150, 300, 450, 600, or 900 mg lifibrol as a single daily dose for 4 weeks. In the second study, patients were randomized to receive either 150, 300, or 600 mg lifibrol for 12 weeks. Efficacy was determined by serial measurements of serum lipids either on a weekly or biweekly basis during each study. RESULTS: Compared with baseline, lifibrol reduced LDL cholesterol (> 40%, p < 0.0001) and apolipoprotein B (approximately 40%, p < 0.0001) by 4 weeks in both studies. After 6 weeks, high-density lipoprotein (HDL) cholesterol levels increased in the placebo and 150 and 300 mg lifibrol groups. In the 600 mg lifibrol group, triglycerides (approximately 25%, p < 0.001), lipoprotein (a) (approximately 30%, p < 0.001), and HDL cholesterol (approximately 5%, p < 0.002) decreased. Lifibrol reduced key sterol intermediates (e.g., lanosterol, lathosterol, beta-sitosterol, and campesterol) and increased serum bile acids, but it had no effect on urinary mevalonic acid excretion. The pharmacokinetics of lifibrol are independent of dose and are similar in men and women. Lifibrol was well tolerated. The most frequent medical event in both studies was skin rash. CONCLUSIONS: Lifibrol is a potent lipid-lowering drug in patients with hypercholesterolemia.

Adolescent↗

PubMed1995

Hematologic effects of a novel hemoglobin-based oxygen carrier in normal male and female subjects.

The objective of this study was to assess the relationship between iron metabolism and pharmacokinetics of hemoglobin-based oxygen carrier-201 (HBOC-201), a polymerized hemoglobin product of bovine origin. A randomized, single-blind, single-dose study design was used. The study was performed at the Upjohn Research Clinics in Kalamazoo, Michigan. Four groups of healthy men and women (n = 24), who either received HBOC-201 (9 men, 9 women) or a control solution (Ringer's lactate) (3 men, 3 women) participated in the study. All subjects had phlebotomy (approximately 15% blood volume) followed by 3:1 hemodilution with Ringer's lactate and an intravenous infusion of HBOC-201 (up to 45 gm or 350 ml) or control solution (Ringer's lactate). Serial arterial blood gas samples with a radial artery catheter and simultaneous pulse oximetry were done during the first 24 hours. Serial samples for serum iron, ferritin, erythropoietin, and plasma HBOC-201 levels were taken over a 1-month period. In the HBOC-201-treated groups, serum iron and ferritin levels increased. Peak serum iron and ferritin levels occurred by hours 8 (up to 220 micrograms/dl) and 48 (up to 180 ng/ml), respectively. Serum iron levels paralleled HBOC-201 concentrations. Plasma half-life of HBOC-201 was about 20 hours. Serum erythropoietin increased by twofold to sixfold over baseline (p < 0.001) at 24 hours. No urinary hemoglobin was detected in the groups with HBOC-201-treated subjects. This study demonstrates that HBOC-201 produces increases in serum iron, ferritin, and erythropoietin that closely parallel plasma levels of HBOC-201 in men and women.

Adult↗

PubMed1994

Pharmacokinetics of cefpodoxime proxetil in healthy young and elderly volunteers.

The influence of age on the pharmacokinetics of cefpodoxime was evaluated in 12 elderly (ages 65-85 years) and 12 weight- and sex-matched young (ages 20-33 years) subjects, each of whom received two cefpodoxime proxetil 200-mg tablets every 12 hours for 14.5 days. Serial blood samples and urine were collected after the first dose on day 1, after the morning dose on day 8, and after the last (morning) dose on day 15. Plasma and urine samples were assayed for cefpodoxime concentrations using HPLC methods. Within each age group, mean pharmacokinetic parameters determined on day 1 were similar to corresponding values on days 8 and 15, indicating that cefpodoxime does not accumulate after twice-daily dosing of cefpodoxime proxetil. Based on this result, parameters were pooled across days in each age group. No significant differences were observed between healthy and elderly volunteers in area under the plasma concentration-time curve for the 12-hour dosing interval, peak plasma concentration, or time to peak concentration. Mean urinary excretion and renal clearance of cefpodoxime were significantly lower in elderly subjects. Differences in renal clearance were attributed to the corresponding age-related reduction that was noted in creatinine clearance values, whereas the lower urinary excretion of cefpodoxime probably reflected slightly reduced systemic drug absorption in the elderly. Differences in these parameters between groups were less than 30%, and were unlikely to be of clinical importance. The data indicate that dose adjustment of cefpodoxime in elderly subjects having normal (age-adjusted) creatinine clearance values is not required.

Adolescent↗

PubMed1994

Lack of effects of beta-carotene on lipids and sex steroid hormones in hyperlipidemics.

Beta-carotene in doses of up to 300 mg daily raises high-density lipoprotein cholesterol levels within 2 to 4 weeks in healthy subjects. The authors, in this study, investigate the short-term effects of high-dose beta-carotene upon serum lipids, lipoproteins, and selected sex steroid hormones in 59 adult patients with Type IIa or IIb hyperlipidemia and 36 healthy subjects. Volunteers took beta-carotene (300 mg) or wheat germ oil capsules daily for 30 days. Lipids were measured on days 1, 14, 21, and 30. Beta-carotene, retinol, free and total testosterone, and estradiol levels were measured on days 1 and 30. Total high-density lipoprotein cholesterol levels increased 10% (p < 0.01) over baseline in all groups by day 14 but returned to baseline by day 30. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels transiently increased between days 14 and 21 by up to 9%, 8%, and 20%, respectively, only in the patients with hyperlipidemia treated with beta-carotene, but returned to baseline on day 30. Apolipoproteins A and B were unchanged. Despite 20-fold increases of plasma beta-carotene levels there, were no reports of carotenodermia and no alteration in sex steroid hormones, retinol levels, hepatic transaminases, or persistent changes in serum lipids that were attributable to beta-carotene.

Adult↗

PubMed1992

Disposition of cefpodoxime proxetil in hemodialysis patients.

The disposition of cefpodoxime after single, oral 200-mg doses of cefpodoxime proxetil (cefpodoxime equivalents) was investigated in an open-label study of six patients with end-stage renal disease currently maintained on hemodialysis. Subjects were randomly assigned to one of two treatment groups, which differed in the sequence of the interdialytic and intradialytic periods. Doses were separated by at least 2 weeks. Blood samples were serially collected for 48 hours after each treatment; if obtainable, urine was also collected over this same period. During the intradialytic period, hemodialysis was scheduled to begin approximately 3 hours after dosing, and dialysate was collected before and until the end of dialysis. Average cefpodoxime elimination half-life for the interdialytic period was 18.0 +/- 6.5 hours; apparent total body clearance was 28.6 +/- 13 mL/minute. The half-life during hemodialysis, 2.66 +/- 0.74 hours, was considerably shorter than that after hemodialysis, 19.2 +/- 3.5 hours, in the intradialytic period of the study. Hemodialysis clearance of cefpodoxime was 120 +/- 31 mL/minute, which was 57.1 +/- 13% and 71.7 +/- 25% of the hemodialysis clearance for urea nitrogen and creatinine, respectively. The 2.86 +/- 0.25 hour hemodialysis session removed 22.4 +/- 2.9% of the administered dose, as assessed by cefpodoxime recovery in dialysate. A maximum rebound in cefpodoxime plasma concentration of 0.41 +/- 0.33 mcg/mL was observed, at about one-half hour after the end of hemodialysis. Based on these results, dosage adjustment is not required, but extension of the dosing interval is warranted.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function.

The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h.

Acute Kidney Injury↗

PubMed1992

Synergistic effects of oral nonsteroidal drugs and topical corticosteroids in the therapy of sunburn in humans.

The ability to modify skin injury due to ultraviolet light (UVB) by the nonsteroidal anti-inflammatory drugs (NSAIDs) oral ibuprofen (IB) or indomethacin (IN) plus topical betamethasone dipropionate (BD) was studied in 24 subjects in this open-label, four-way, cross-over trial. All subjects received UVB at weekly intervals: group 1 was randomized to IB, BD, IB + BD or control, and group 2 to IN, BD, IN + BD or control. Oral medications were given prior to and after exposure to UVB, but BD was applied only afterwards. The skin response to UVB [erythema and increased skin blood flow (SBF)] was measured serially for 96 h. A skin biopsy was taken at 24 h after each dosing with UVB. At maximum erythema (8-12 h after UVB), the following approximate reductions in SBF (compared to control responses) were noted: 42-58% for combination therapies, 33-40% for IB or IN alone, and 17% for BD alone. SBF tended to equalize across all treatments by 24 h and remained until 96 h. Skin biopsy results were consistent with the noninvasive findings. Thus, we observed a synergistic effect of reduction of UVB-induced erythema and SBF with combinations of oral NSAIDs and topical corticosteroids. This study could have implications for the therapy of sunburn in humans.

Administration, Oral↗

PubMed1992

A double stopcock technique for repeated sampling of venous blood.

Repeated sampling for measurement of venous blood levels of hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen with a novel method of phlebotomy, the double stopcock technique (DST), was compared to heparin lock (HPL), Angiocath with obturator (AOB) and direct venipuncture (DVP) techniques. There were 12 normal subjects in this randomized, three-way crossover trial. During each portion of the crossover, simultaneous samples for hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen were taken from each phlebotomy site prior to and after oral dosing with 400 mg ibuprofen. The DST was the best acceptable method based on the assessment of comfort by the subjects, followed by the AOB, HPL and DVP techniques. The least amount of blood waste was with the DST. The degree of hemolysis (as shown by plasma hemoglobin and potassium) was comparable across all techniques. Across all of the techniques, measurement of hemoglobin, hematocrit and ibuprofen levels using DST, HPL and AOB yielded lower levels than DVP. These changes were small and were not clinically significant, although statistically significant in some cases. The authors conclude that when there is need for frequent, rapid and repetitive venous blood sampling with minimal blood wastage and patient discomfort, the DST should be considered.

Blood Specimen Collection↗

PubMed1991

Pharmacokinetic and tolerance studies of cefpodoxime after single- and multiple-dose oral administration of cefpodoxime proxetil.

Cefpodoxime proxetil, a third generation, broad-spectrum, oral cephalosporin, was administered in single doses of 100, 200, 400, 600, and 800 mg (dose expressed as cefpodoxime equivalents) and multiple doses of 100, 200, and 400 mg twice daily to healthy volunteers. The pharmacokinetics of the active metabolite, cefpodoxime, and tolerance of cefpodoxime proxetil were determined. Results from the single-dose study indicate that cefpodoxime exhibits nonlinear pharmacokinetics over the dose range of 100 to 800 mg. This nonlinearity is primarily due to differences in dose-normalized AUC and Cmax, urinary recovery, and half-life between one or more of the higher-dose treatment groups and the 100-mg dosing group. After multiple-dose (twice daily) administration for 15 days, steady state is achieved on the second day of dosing, and there is no drug accumulation. Cefpodoxime pharmacokinetics are linear with dose over the clinically relevant dosing range of 100 to 400 mg. Microbiologic and HPLC plasma assay results are highly correlated, with close agreement between HPLC- and microbiologic-determined pharmacokinetic parameter estimates. Cefpodoxime proxetil was well tolerated in both studies. The most frequent medical events were related to gastrointestinal problems and consisted of transient loose stools in three subjects in the single-dose study and antibiotic-associated diarrhea in one subject in the multiple-dose study.

Administration, Oral↗

PubMed1991

Effects of fish oil and endorphins on the cold pressor test in hypertension.

The effects of fish oil and naloxone on blood pressure, catecholamines, and endorphins during the cold pressor test were evaluated in a randomized, double-blind, placebo-controlled, two-way crossover trial of normotensive and medication-free hypertensive men (n = 13 each). Subjects were given 5 gm omega-3 fatty acids per day or placebo for 30 days with a 1-month washout between interventions. The cold pressor test (hand in ice water for 5 minutes) was done at the end of the treatment periods. Intravenous naloxone (10 mg) or placebo was given before the cold pressor test. Fish oil-treated, normotensive, or hypertensive groups had similar changes in blood pressure, plasma catecholamine levels, and beta-endorphins during the cold pressor test, but naloxone treatment was associated with fivefold and tenfold increases in plasma epinephrine and cortisol levels, respectively. Naloxone may modulate sympathomedullary discharge through blockade of endorphin activity. It is unlikely that endorphins are involved in the blood pressure increase during the cold pressor test or that fish oil alters this response.

Adult↗

PubMed1991

Beta-carotene's effects on serum lipoproteins and immunologic indices in humans.

Doses of beta-carotene for cancer-prevention trials have been chosen based on epidemiologic data. Mechanisms of the putative antineoplastic effects by beta-carotene are unknown but may involve modulation of the immune system. We measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45, 180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled, open-label, parallel study. Plasma beta-carotene concentrations were markedly increased by 2 wk and were correlated with dose. Beta-carotene concentrations plateaued between 2 and 4 wk except for the 300-mg group. Thus, we developed a dose-concentration curve to optimize beta-carotene-dose selection to achieve target plasma concentrations. We were unable to identify any effects of beta-carotene ingestion on the immunologic indices studied, but modest increases in high-density-lipoprotein cholesterol were observed in all beta-carotene-treated groups.

Adult↗

PubMed1990

The effect of ketoconazole and transdermal estradiol on serum sex steroid hormones levels.

In this randomized, open-label trial, 24 subjects were studied. There were 12 subjects with essential hypertension and 12 normotensive controls who received, after an initial control period, 48 h of treatment with a transdermal estradiol patch or ketoconazole tablets every 8 h for six doses, or in combination. LHRH (100 micrograms) and ACTH (250 micrograms) were given at 48 h of each treatment. Each treatment was one week apart. In both normotensive and hypertensive men ketoconazole reduced adrenal and gonadal androgens, raised 11-deoxycortisol and 17 alpha-hydroxyprogesterone levels; blunted the rise of cortisol to ACTH and had no effect on the response of LH to LHRH. Transdermal estradiol raised serum estradiol levels, blunted the time to peak plasma concentration of LH to LHRH and produced a normal response to ACTH. Although baseline level of total and free testosterone and DHEA-S were lower in hypertensive men, the response of the pituitary (LH) to LHRH and adrenal axis with ACTH were similar in both normotensive and hypertensive men. Blood pressure was unaffected by any of the treatment interventions in either normotensive or hypertensive men. Although ketoconazole or transdermal estradiol reduce androgens, there was no evidence that this reduction in androgens was involved with the short term regulation of blood pressure in hypertensive men.

Administration, Cutaneous↗

PubMed1990

Fish oil produces an atherogenic lipid profile in hypertensive men.

The effects of fish oil supplements on plasma and platelet membrane lipids, lipoproteins, sex steroid hormones, glucose, insulin, platelet aggregation, and blood pressure in normal subjects (n = 13) and patients with essential hypertension (n = 13) were studied in this randomized, double-blind, placebo-controlled, two-way crossover study. Treatments consisted of 30 days of 5 g of n-3 fatty acids (ten 1-g capsules of fish oil daily) or placebo capsules (ten wheat germ oil capsules daily) with a one-month washout in between each crossover. Serum lipids and lipoproteins were measured before dosing and every two weeks during the study. Sex steroid hormones, glucose, insulin, and fatty acid composition in platelet membrane phospholipids were measured before dosing and at the end of each crossover. During treatment with fish oil, only the hypertensive had increases in total cholesterol (8%, p less than 0.026), LDL cholesterol (19%, p less than 0.006) and apolipoprotein B (18%, p less than 0.026). Serum androgens (total and free testosterone) were 30% lower in hypertensives than normotensives before any dosing, but were unchanged with placebo or fish oil capsules in either group. Plasma glucose, insulin, platelet aggregation, and the incorporation of n-3 fatty acids into platelet membrane phospholipid subfractions were similar in both normotensive and hypertensive men. Blood pressure was not affected by fish oil treatment in either group of men. These results provide evidence that fish oil may adversely affect serum lipids to yield an atherogenic lipid profile in hypertensive men.

Adult↗

PubMed1990

Pharmacokinetics of cefpodoxime in plasma and skin blister fluid following oral dosing of cefpodoxime proxetil.

The single-dose and steady-state pharmacokinetics of cefpodoxime were assessed in plasma and skin blister fluid (SBF) after oral dosing of 200 mg (n = 8) and 400 mg (n = 8) of cefpodoxime proxetil (doses are expressed as cefpodoxime equivalents) in healthy subjects in an open-label, parallel-design study. Skin blisters were formed by air suction on the midvolar forearm by a previously validated method. After single-dose administration, serial plasma and SBF samples were collected over 24 h for measurement of cefpodoxime by microbiological assays. After a 1-week washout, subjects received the same doses of antibiotic every 12 h for 5 days, with plasma and SBF sampling on day 5. After 200 mg of cefpodoxime proxetil, average peak concentrations (Cmax) in plasma and SBF were 2.18 +/- 0.52 and 1.55 +/- 0.59 micrograms/ml, respectively, after a single dose and 2.33 +/- 0.74 and 1.56 +/- 0.55 micrograms/ml, respectively, at steady state. After 400 mg of cefpodoxime proxetil, Cmax in plasma and SBF averaged 4.16 +/- 1.04 and 2.94 +/- 0.71 micrograms/ml, respectively, following a single dose and 4.10 +/- 0.95 and 2.84 +/- 0.88 micrograms/ml, respectively, at steady state. Cmax occurred 1.1 to 1.6 h later in SBF than in plasma. There was no accumulation of cefpodoxime in plasma or SBF when dosing was done every 12 h. Cefpodoxime blister fluid penetration was estimated to be 67 to 101%, consistent with the relatively low serum protein binding of the drug. Cefpodoxime levels exceeding the MIC for 90% of many skin pathogens, such as Streptococcus species (<1 microgram/ml) or Staphylococcus species (2 to 4 micrograms/ml), were achieved in plasma and SBF following the 200- and/or 400-mg dosing regimens.

Administration, Oral↗

PubMed1990

New methods to detect the effect of alteration in gastric pH and intestinal transit by metoclopramide and propantheline using a continuous gastric pH probe and hydrogen breath analysis.

UNLABELLED: The effects of oral doses of metoclopramide (M, 10 mg) and propantheline (P, 30 mg) on alteration in gastric pH and emptying were determined using a continuous pH probe (Digitrapper, Synectics) and hydrogen breath analysis (HBA, QuinTron) in eight male subjects. The four phases consisted of HBA, HBA and pH probe, and HBA and pH probe and either P or M. Baseline pH measurements were recorded for 60 min prior to dosing with 10 g of lactulose in three of the periods. Dosing with P or M was given 30 min before administration of lactulose. HBA and continuous gastric pH were measured for 120 min. M produced earlier and higher peak hydrogen concentration than control (p less than 0.0001). P decreased peak hydrogen and increased gastric pH from approximately 2.0 to 4.0 (p less than 0.0001). CONCLUSIONS: 1) HBA can be used to detect alterations of intestinal motility; 2) The gastric pH probe produces a small increase in intestinal motility; and 3) The combination of the gastric pH probe and HBA could be a useful technique to simultaneously evaluate gastric pH and gastrointestinal motility.

Adult↗

PubMed1990

Gastric emptying and the pharmacokinetics of the cephalosporin antibiotic, cefpodoxime proxetil.

The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug.

Adolescent↗