Search PubMed⌕ Search

Biomedical subjects

G C Yee

Publications and source records attributed to G C Yee.

At least 19 recordsLinked to original sources
PubMed2007

Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects.

Limited data are available about the effect of steady-state lopinavir and ritonavir (LPV/r) on bupropion pharmacokinetics. As patients may benefit by using these two agents in combination, this study determined the extent and direction of this drug-drug interaction. Twelve healthy volunteers received a single 100 mg dose of sustained-release bupropion before and after 2 weeks of treatment with LPV/r 400 mg/100 mg twice daily. Pharmacokinetics profiles were determined on days 1 and 30 for bupropion and hydroxybupropion and days 29 and 30 for LPV/r. LPV/r administration significantly decreased bupropion maximum plasma concentration (C(max)) by 57% (90% confidence interval (CI), 38-76%; P<0.01) and area under the curve (AUC) infinity by 57% (90% CI, 32-83%; P<0.01). Hydroxybupropion C(max) and AUC infinity decreased by 31% (90% CI, 7-55%; P<0.01) and by 50% (90% CI, 34-65%; P<0.01), respectively. No significant changes in the pharmacokinetics of LPV/r were found following administration of a single dose of bupropion. Concurrent use of LPV/r and bupropion resulted in decreased exposure to bupropion and its active metabolite hydroxybupropion that may necessitate as much as a 100% dose increase of bupropion. A probable mechanism for this interaction is the concurrent induction of cytochrome P450 2B6 and UDP-glucuronosyltransferase enzymes. LPV/r exposure is unaffected by a single dose of bupropion.

Adult↗
PubMed2001

Topotecan-filgrastim combination is an effective regimen for mobilizing peripheral blood stem cells.

We compared the efficacy, toxicity, and cost of topotecan-filgrastim and filgrastim alone for mobilizing peripheral blood stem cells (PBSCs) in 24 consecutive pediatric patients with newly diagnosed medulloblastoma. PBSCs were mobilized with an upfront window of topotecan-filgrastim for 11 high-risk patients (residual tumor > or =1.5 cm2 after resection; metastases limited to neuraxis) and with filgrastim alone for 13 average-risk patients. All patients subsequently underwent craniospinal irradiation and four courses of high-dose chemotherapy with stem cell rescue. Target yields of CD34+ cells (> or =8 x 10(6)/kg) were obtained with only one apheresis procedure for each of the 11 patients treated with topotecan-filgrastim, but with a mean of 2.3 apheresis procedures for only six (46%) of the 13 patients treated with filgrastim alone (P = 0.0059). The median peak and median total yield of CD34+ cells were six-fold higher for the topotecan-filgrastim group (328/microl and 21.5 x 10(6)/kg, respectively) than for the filgrastim group (54/microl and 3.7 x 10(6)/kg, respectively). Mean times to neutrophil and platelet engraftment were similar. Myelosuppression was the only grade 4 toxicity associated with topotecan-filgrastim mobilization and lasted a median of 5 days. Compared with filgrastim mobilization, topotecan-filgrastim mobilization resulted in a mean cost saving of $3966 per patient. Topotecan-filgrastim is an efficacious, minimally toxic, and cost-saving combination for PBSC mobilization.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Economic analysis of four triple regimens for the treatment of Helicobacter pylori-related peptic ulcer disease in in-patient and out-patient settings in Hong Kong.

BACKGROUND: One-week triple regimens have been shown to be effective for the treatment of Helicobacter pylori-related peptic ulcer disease. AIM: To conduct an economic analysis of four triple regimens for the treatment of H. pylori-related peptic ulcer disease from the perspective of a public health organization in Hong Kong. METHODS: Records of 200 patients with H. pylori-related peptic ulcer disease, who had previously participated in a randomized comparison of ranitidine bismuth citrate (RBC) with amoxicillin and clarithromycin (RAC), omeprazole with amoxicillin and clarithromycin (OAC), RBC with metronidazole and tetracycline (RMT), or, colloidal bismuth subcitrate with metronidazole and tetracycline (BMT) in either in-patient or out-patient setting were reviewed. RESULTS: Fifty patients were excluded because of incomplete documentation or lack of peptic ulcer. In the out-patient group (n=72), the median direct costs of the RAC group (HK $ 5094) were lower those of the BMT (HK $ 5400), RMT (HK $ 5394), or OAC (HK $ 5440) groups, but the difference was significant only between the RAC and BMT groups (P < 0.05). In the in-patient group (n=78), the median direct costs of the RMT group (HK $ 8524) were significantly lower than those of the OAC (HK $ 13 871) and RAC (HK $ 12 092) groups (P < 0.05), but were similar to those of the BMT group (HK $ 8758). CONCLUSIONS: RAC and RMT are the least costly regimens for out-patient and in-patient treatment, respectively, of H. pylori-related peptic ulcer disease in Hong Kong.

Adolescent↗
PubMed1997

Cost-utility analysis of taxane therapy.

A cost-utility analysis of docetaxel versus paclitaxel in patients with anthracycline-resistant metastatic breast cancer was reviewed. Cost-utility analysis provides estimates of the additional cost of a new therapy per quality-adjusted life-year (QALY) saved or gained. Utility scores measure the strength of a patient's preference for a given health state or outcome. Few studies have evaluated preferences in patients receiving cancer treatment. Since docetaxel may represent an advance in the management of anthracycline-resistant recurrent metastatic breast cancer, a decision-analysis model was developed to evaluate the pharmacoeconomics of this drug versus those of paclitaxel. Although the overall treatment costs of docetaxel were slightly higher than those of paclitaxel, docetaxel was associated with a gain of 0.0905 QALY per patient. This gain in QALYs is equivalent to 33 days of perfect health, which represents a substantial proportion of the life expectancy of one of these patients (typically no longer than nine months). The incremental cost-utility ratio associated with docetaxel therapy was estimated to be $4011 per QALY. Compared with paclitaxel, docetaxel for anthracycline-resistant metastatic breast cancer is within the acceptable range of cost-effectiveness ratios for most medical interventions. Cost-utility analysis is a valuable technique for evaluating new antineoplastic regimens that offer some treatment benefit but do not prolong survival compared with other therapeutic options.

Animals↗
PubMed1997

The true cost of bone marrow transplantation.

Bone marrow transplantation is an example of a highly technical therapy that offers hope to patients with bone marrow failure or various malignancies. Bone marrow transplantation is much more costly "up-front" but perhaps not more costly long-term than alternative therapies. Although economic analyses appear relatively simple, interpretation and use can be problematic. Several economic analyses have identified complications that occur frequently and affect the reported cost-effectiveness of high-dose chemotherapy. Efforts to reduce the cost of bone marrow transplantation have focused on new strategies to more effectively control these complications. The introduction of new technologies to speed engraftment, to improve patient selection methods, and the shifting of care to outpatient settings all have resulted in significant reductions in duration of hospital stay, treatment-related mortality, and costs. More studies of long-term outcomes are needed for transplant and nontransplant treatment options to guide present and future applications of this treatment option.

Ambulatory Care↗
PubMed1997

Applied pharmacoeconomics. When can publication be legitimately withheld?

Pharmacoeconomic studies can help decision-makers choose the most efficient drug treatments in our internationally cost-constrained healthcare environment. However, perceptions of bias about the nature of many economic evaluations limit the usefulness of pharmacoeconomic data to decision-makers. In an effort to increase the credibility of pharmacoeconomic studies, several groups have developed methodological guidelines, and one has developed ethical guidelines for these evaluations. In this article, we evaluate issues related to the publication of the results of pharmacoeconomic studies. Pharmacoeconomics is a true science (and should be so treated), rather than a form of marketing. Pharmacoeconomic studies must undergo the same peer review process and be published in serious research journals, as are other types of scientific investigations. Investigators should attempt to publish the results of pharmacoeconomic studies, even (and, perhaps, especially) when the results are not favourable to the sponsor. However, there are acceptable reasons to withhold publication of 'negative' results. For example, when methodological problems plague a study, or when the study addresses an investigational drug not likely to be approved, then researchers are justified in giving up on publication, if they so choose. Similarly, feasibility studies to test methods of data collection or analyses conducted very early in the drug development process need not always be published. Nonetheless, access to all important investigations--regardless of whether the results are positive or negative--will become more important as healthcare becomes more evidence-based, as decisions have impact on large populations of people, and as those in charge of formularies actually begin to use cost-effectiveness analysis to help make choices among competing drugs.

Economics, Pharmaceutical↗
PubMed1995

Effect of grapefruit juice on blood cyclosporin concentration.

Grapefruit juice increases blood concentrations of some dihydropyridine calcium-channel blockers, which are metabolised by the P450 enzymes that also metabolise cyclosporin. We evaluated, in a randomised cross-over study, the effect of grapefruit juice on blood cyclosporin concentrations in 14 healthy adults. Each subject was given oral cyclosporin 300 mg with 250 mL grapefruit juice, orange juice, or water. Area-under-the-curve (AUC) was significantly higher with grapefruit juice than with water or orange juice (means 7057, 4871, and 4932 ng h/mL, respectively; p < 0.0001). Thus grapefruit juice may provide a non-toxic and inexpensive alternative to drugs that are used to reduce cyclosporin dose.

Adolescent↗
PubMed1992

Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods.

We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients.

Adult↗
PubMed1992

Stability of cyclosporine in dextrose 5%, NaCl 0.9%, dextrose/amino acid solution, and lipid emulsion.

OBJECTIVE: Because of limited intravenous access in patients who have undergone bone marrow transplant (BMT), we undertook a study to determine the safety of mixing cyclosporine in intravenous preparations commonly administered to BMT patients. DESIGN: In a pilot study, we investigated the stability of intravenous cyclosporine (Sandimmune) in four types of intravenous fluids: dextrose 5%, NaCl 0.9%, dextrose/amino acid solutions, and lipid emulsion. Because the pilot study showed highly variable cyclosporine concentrations that suggested inadequate mixing, we undertook another study to determine the effect of the mixing method on cyclosporine concentrations. OUTCOME MEASURE: Cyclosporine was considered stable in the study solutions if concentrations remained above 90 percent of the initial concentrations. RESULTS: Substantial variation in cyclosporine concentrations was observed in lipid emulsion and dextrose/amino acid solutions and gentle swirling of the solutions was insufficient to adequately disperse the drug. The variation was eliminated by vigorous shaking either before each sampling or once after the initial addition of cyclosporine. We used vigorous shaking methods to establish that cyclosporine is stable for up to 72 hours at room temperature in dextrose 5%, 10% amino acid solution with dextrose 50%, and Liposyn 10%, and up to 8 hours in NaCl 0.9%. CONCLUSIONS: These data may be used to simplify cyclosporine administration in patients who have limited intravenous access.

Amino Acids↗
PubMed1992

Hematopoiesis.

Hematopoiesis begins with the pluripotent stem cell in the marrow and culminates in mature, functional red blood cells, white blood cells, and platelets in the circulation. The process consists of a complex and well-orchestrated sequence of cell proliferation, differentiation, and maturation, that is stimulated and regulated by a host of cytokines and hormones. The various growth factors act individually and in concert at different stages of hematopoiesis and have important effects on mature cell function.

Blood Platelets↗
PubMed1991

Recent advances in cyclosporine pharmacokinetics.

Although cyclosporine has been in clinical use for more than a decade, many questions persist concerning its pharmacokinetics. Gastric emptying, bile acids, and gastrointestinal motility can influence drug absorption after oral administration, but the relative importance of each of these factors and their interactions as determinants of absorption are not clear. The fraction unbound in plasma has been determined in several studies and may be associated with clinical effects. Biochemical and molecular studies have identified the specific cytochrome P-450 enzymes that metabolize cyclosporine to its primary metabolites. The drug's basic pharmacokinetic profile has been defined and many factors have been identified that can influence clearance, such as age, hepatic function, hematocrit, and lipoprotein concentrations. With the development of sensitive and specific analytical methods, many new cyclosporine metabolites have been identified in humans. The major metabolites are present in relatively high concentrations in human blood and have some immunosuppressive activity in vitro, but their contribution to in vivo immunosuppression is not clear.

Adolescent↗
PubMed1991

Dosage forms of cyclosporine.

Cyclosporine can be given intravenously or orally, as a solution or soft gelatin capsule. Because of the drug's poor water solubility, ethoxylated plant fats and ethanol are added to the commercially available dosage forms.

Administration, Oral↗
PubMed1990

Pharmacokinetic drug interactions with cyclosporin (Part I).

This article reviews the reported pharmacokinetic interactions between cyclosporin and other drugs. Both rifampicin and the majority of anticonvulsants can decrease cyclosporin concentrations to levels that are at or below the limit of detection for most assays. There have been no reports of any interaction between valproic acid and cyclosporin. Other drugs that have been reported to decrease cyclosporin concentration include sulfadimidine and trimethoprim, nafcillin and octreotide. Erythromycin, ketoconazole and some calcium channel blockers have been clearly shown to increase the concentration of cyclosporin. Other less well documented interactions have been reported with other macrolide antibiotics, other azole antifungal drugs, high dose methylprednisolone, metoclopramide, fluoroquinolones, imipenem/cilastatin, oral contraceptives/danazol, sulindac, methyltestosterone, colchicine, acetazolamide, alcohol and cimetidine. Although the most commonly reported mechanism is inhibition of cyclosporin metabolism, there is increasing evidence that erythromycin, metoclopramide and probably other drugs increase the bioavailability of oral cyclosporin. Two calcium channel blockers which have not been reported to interact with cyclosporin are nifedipine and nitrendipine. With increasing use of cyclosporin, the number of drugs reported to interact will rise. Prudent clinicians should monitor the concentration of this agent more frequently when another drug is added or discontinued and cyclosporin dosage should be adjusted when appropriate. Sustained changes in cyclosporin concentration can result in graft rejection (or graft-versus-host disease) or renal toxicity. Further studies are needed to determine the mechanism of most of these interactions.

Animals↗
PubMed1990

Pharmacokinetic drug interactions with cyclosporin (Part II).

Part I of this article, which appeared in the previous issue of the Journal, considered the potential mechanisms of drug interactions with cyclosporin, and divided the interacting drugs into 2 categories. Drugs that decrease cyclosporin concentrations (e.g. anti-convulsants, rifampicin, etc.) were dealt with first; the authors then moved on to consider the second category, those that increase cyclosporin concentration (macrolide antibiotics, azole antifungal drugs). Part II continues the survey of this category.

Calcium Channel Blockers↗