As an applied science, pharmacokinetics permits the clinician to predict serum drug concentrations (SDCs) and associated pharmacologic responses, estimate dosage requirements, and assess unexpected drug responses. Therapeutic drug monitoring operationalizes the principles of pharmacokinetics through a multidisciplinary approach to the assessment and application of patient SDC data. Complicating the assessment of patients receiving these drugs is the tendency for physiologic changes and drug interactions to influence SDCs and associated pharmacologic responses. In determining the best dosing regimen for a particular patient, it is important to consider factors such as age, weight, major organ function, and concurrent drugs and disease states.

Age Factors↗

PubMed1990

Haemothorax caused by a solitary costal exostosis.

A case of spontaneous haemothorax in a 14 year old boy due to trauma to the diaphragm caused by a solitary benign growth (exostosis) of a rib is described.

Adolescent↗

PubMed1988

Pharmacokinetics of sufentanil in patients undergoing renal transplantation.

Renal failure and chronic haemodialysis are often associated with alterations in fluid status and plasma proteins. These changes, in turn, may result in pharmacokinetic alterations in affected patients. The purpose of this study was to investigate the pharmacokinetics of sufentanil in chronic renal failure patients undergoing kidney transplantation. Ten male patients were studied. Following induction of anaesthesia each patient received sufentanil 2.0 micrograms.kg-1 IV with subsequent serial plasma sampling for drug measurement from one to 360 minutes. A biexponential equation provided the best fit of the sufentanil concentration data with mean +/- SEM distribution (alpha) and elimination (beta) half-lives of 2.9 +/- 1.3 and 176 +/- 87 minutes, respectively. The mean Vc and Vd beta values were 0.15 +/- 0.05 L.kg-1 and 0.85 +/- 0.16 L.kg-1, respectively; plasma drug clearance was 11.5 +/- 3.7 ml.kg-1.min-1. Mean values for K10, K12 and K21 were 0.15 +/- 0.06.min-1, 0.4 +/- 0.14.min-1 and 0.1 +/- 0.04.min-1, respectively. With the exception of Vd beta, these pharmacokinetic values are similar to those reported in previous studies in general surgical, elderly and burn patients. The Vd beta values observed in this study may have resulted from alterations in drug distribution or elimination following revascularization of the implanted kidneys. Nevertheless, it appears that modification of sufentanil doses is unnecessary in chronic renal failure patients undergoing renal transplantation.

Adult↗

PubMed1988

Comparative bioavailability of two oral sustained-release procainamide products.

The bioavailability characteristics of two sustained-release oral procainamide preparations, Procan SR and Pronestyl-SR, were compared in 10 patients with arrhythmias. Each patient was randomly assigned to receive either Procan SR 1 g or Pronestyl-SR 1 g, both administered orally every six hours. The initial drug was continued for 48 hours (eight doses), at which time the second drug, given at the same dosage and dosing interval, was substituted for a 48-hour period. Serum samples for procainamide determination were obtained hourly between 42 and 48 and between 90 and 96 hours after initiation of procainamide therapy. Values for area under the serum concentration-time curve (AUC) during the steady-state dosing interval, maximum serum drug concentration (Cmax), minimum serum drug concentration (Cmin), Cmax:Cmin ratio (representing fluctuations in serum drug concentrations within the dosing interval), and the time to maximum serum drug concentration (tmax) were determined. Mean ( +/- S.D.) tmax values for Procan SR and Pronestyl-SR were 2.2 +/- 0.8 hours and 3.8 +/- 1.1 hours, respectively. Only the differences between tmax values were statistically significant. The study had an 83% chance of detecting a 20% difference in AUC values. The chances of detecting a 20% difference in values for Cmax and Cmin were 62% and 71%, respectively. These two preparations would probably possess similar therapeutic properties when given at the same dosage and dosing schedule; however, studies with larger subject populations are needed to project bioavailability data to the general population.

Aged↗

PubMed1987

Intragastric pH monitoring in acute upper gastrointestinal bleeding and the effect of intravenous cimetidine and ranitidine.

Intragastric pH was measured continuously from 1800 to 1200 hours the following day in 22 duodenal ulcer patients and in eight gastric ulcer patients, all of whom had been admitted as emergencies with acute upper gastrointestinal haemorrhage. The effects of intravenous cimetidine or ranitidine were compared with no treatment. In patients with duodenal ulcer, median intragastric pH was 1.8 (range 1.0-4.9) in the group receiving no treatment. In the cimetidine group (400 mg, 6-hourly, n = 8) median pH was 4.7 (range 1.5-7.7) and after ranitidine (50 mg, 6-hourly, n = 10) it was 3.8 (range 1.2-7.8). The pH remained above 4.0 for 67% of the recording time with cimetidine, 47% with ranitidine and for only 3% with placebo. Intragastric pH in gastric ulcer patients without treatment was higher (median 3.4, range 1.0-6.9) than in duodenal ulcer patients with treatment. Both H2 antagonists raised intragastric pH in patients with gastric ulcer and maintained a gastric pH of greater than 4.0 for at least 50% of the time. Presently recommended i.v. doses of cimetidine and ranitidine do not consistently maintain gastric pH above 4.0 for long periods in patients with peptic ulcer bleeding.

Aged↗

PubMed1987

Gastrointestinal transit of an enteric-coated delayed-release 5-aminosalicylic acid tablet.

Gastrointestinal transit of an enteric-coated, delayed-release 5-aminosalicylic acid tablet radiolabelled with indium-111 has been monitored in a preliminary study with eight healthy subjects using gamma scintigraphy. Gastric emptying of the tablet was delayed by the presence of food in the stomach. Disintegration occurred about 5 hours after the tablet left the stomach. There was close agreement between the tablet disintegration times and the initial detection of drug in the blood. The site of disintegration could be established in most instances; approximately 80% of the doses resulted in drug dispersion within the ascending colon. The coated tablets provide an effective means of drug delivery to the proximal colon.

Adult↗

PubMed1987

Evaluation of an enteric-coated delayed-release 5-aminosalicylic acid tablet in patients with inflammatory bowel disease.

Gastrointestinal transit of an enteric coated delayed release 5-aminosalicylic acid tablet radiolabelled with 111indium has been monitored in a total of 13 patients with Crohn's disease and ulcerative colitis. More than 70% of the tablets disintegrated in the small intestine, on average 3.2 hours after emptying from the stomach. Dispersed preparation was detected in the proximal colon of all the patients, except one with an ileostomy. Mean peak plasma concentrations of 5-aminosalicylic acid and its metabolite acetyl-5-aminosalicylic acid occurred 3-4 hours after gastric emptying. The tablets provide a reliable means of drug delivery to the ileum and proximal colon.

Adult↗

PubMed1987

Clearance of continuous intravenous morphine for severe cancer pain.

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15-275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of less than or equal to 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.

Female↗

PubMed1987

Pharmacokinetic comparison of intranasal, oral, and intramuscular metoclopramide in healthy volunteers.

This was a randomized, crossover study of the bioavailability and pharmacokinetics of metoclopramide given by intranasal (IN), oral (PO), and intramuscular (IM) routes. The formulations tested were 5 and 10 mg of IN gel, 10 mg PO, and 5 mg IM. The findings showed that metoclopramide follows similar absorption and elimination characteristics when given via these three extravascular routes. There were no statistically significant differences in the area under the drug concentration versus time curve (AUC) or peak metoclopramide plasma concentration (Cmax) data following PO, IM, or 10-mg IN administration. However, the 5-mg IN doses achieved an AUC that was 39.5% the AUC of the 10-mg IN dose. These data show consistent and relatively predictable metoclopramide plasma concentrations following IN administration. Further, 10-mg doses of IN and PO metoclopramide appear to be bioequivalent.

Administration, Intranasal↗

PubMed1986

Colonic motility and enema spreading.

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents.

Adult↗

PubMed1986

Whole-bowel transit in patients with the irritable bowel syndrome.

The transit of radiolabelled preparations through the stomach, small intestine and colon was monitored in ten patients with the irritable bowel syndrome. Five patients complained of diarrhoea, and five complained of constipation. The preparations comprised a non-disintegrating capsule and a multiparticulate system. Both preparations emptied from the stomach together and at the same rates in both groups of patients. In the patients complaining of constipation, the transit times through the small intestine were the same for both preparations. In the patients complaining of diarrhoea, the capsule passed through the small intestine slightly faster than the particles, but there were no significant differences in the small-intestinal transit rates of the two patient groups. Within the colon, the transit of the capsule was faster than that of the small particles. Although movement through the colon was, on average, faster in the group of patients complaining of diarrhoea, there was considerable intersubject variability, and the differences in transit rates between the two patient groups were not statistically significant.

Adult↗

PubMed1986

131I and 111In-labelled monoclonal antibody imaging of primary lung carcinoma.

Preliminary clinical studies have been carried out to determine whether the monoclonal antibody 791T/36 would localize in primary lung cancer to an extent sufficient for external detection by gamma scintigraphy. Radiolabelling of the antibody with 131I permitted visualization of three out of eight (38%) tumours using planar imaging with 99Tcm-labelled blood pool subtraction. Radiolabelling of the same antibody with 111In permitted visualization of tumour uptake in nine out of 13 (69%) tumours, without the need for image subtraction. Single photon emission computed tomography (SPECT) studies of seven patients demonstrated concentration of 111In-labelled antibody at the tumour site in each case, four of which were visualized on the planar images. The present study demonstrates localization of the 791T/36 antibody in primary lung carcinoma and confirms the superiority of 111In over 131I as a radiolabel for antibody imaging, especially when emission tomography is performed. These data indicate that further work will be required to determine whether this antibody will be a suitable carrier for cytotoxic agents in the therapy of lung cancer.

Aged↗

PubMed1986

24-hour intragastric pH: continuous monitoring or nasogastric aspiration?

Hourly gastric aspiration has commonly been used to assess the efficacy of antisecretory compounds. We have compared continuous ambulatory 24-hour pH monitoring using a radiotelemetry capsule with standard nasogastric aspiration. Eight studies were performed on four male duodenal ulcer patients in remission receiving either placebo or an antisecretory agent. A significant correlation was found between capsule and aspirate pH measurements (r = 0.88, p less than 0.01). Radiotelemetry capsule measurements clearly showed the onset of action of an antisecretory drug, and the buffering effect of food. Radiotelemetric pH monitoring is shown to be as good as gastric sampling in the measurement of 24-hour intragastric acidity, allows continuous measurement of pH during normal activity and can accurately assess the effect of drugs on gastric acidity.

Anti-Ulcer Agents↗

PubMed1985

Piperacillin in colorectal surgery.

Explore the source record for details and available documents.

Abscess↗