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R Kuwabara

Publications and source records attributed to R Kuwabara.

6 recordsLinked to original sources
PubMed2001

Survival and viral load in four groups of HIV-1 infected hemophiliacs compared by three-way data clustering.

We assigned a total of 131 hemophiliacs infected with HIV-1 into four clusters by applying a 3-way data analysis method. Sequentially acquired CD4+ and CD8+ cell counts obtained longitudinally over an observation period from 1986 to 1992 were analyzed. During the successive observation in this interval, a clustering of patients is not always coincident over all the times, because the cell counts vary with time. Therefore, the 3-way data clustering is to obtain the optimal result of the classification of patients through all the interval of observation. Examining patients' survival after that period, the cumulative mortality rate was highest among the 36 hemophiliacs in Cluster 1. Less mortality was found in Cluster 2, consisting of 49 hemophiliacs and none was reported in Clusters 3 and 4, which included 33 and 13 hemophiliacs, respectively. However, a significantly lower blood viral copy number was found in Cluster 3 than in Cluster 4. A total of six long-term non-progressors was found, five in Cluster 3 and one in Cluster 4, while none was found in Cluster 1 or 2. As demonstrated in this analysis, 3-way data clustering may represent a good data mining technique for handling various types of clinical data.

CD4 Lymphocyte Count↗
PubMed2000

Pharmacokinetic consideration on administration regimen of lamivudine in japanese patients infected with HIV-1.

OBJECTIVE: The typical regimen for lamivudine is 150 mg bis in die (bid). However, pharmacokinetic values of lamivudine will differ among individual patients. In addition, few studies regarding the pharmacokinetics of lamivudine in the Japanese people have so far been reported. Therefore, we have aimed to examine the variation in the pharmacokinetic values of lamiduvine present in six Japanese patients with HIV-1 infection. PATIENTS AND METHODS: Lamivudine concentrations were measured in three hemophiliacs (HIV-1-asymptomatic carrier, AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS-related complex, ARC). In order to simulate the lamivudine plasma concentrations found in chronic oral administration, we added an absorption compartment to the two-compartment model. RESULTS: The mean +/- SD of Tmax, Cmax, AUC(0 - infinity) and t1/2beta were 1.2 +/- 0.5 (hours), 1,280 +/- 267 (ng/ml), 6,778 +/- 2,763 (ng x h/ml), and 10.3 +/- 4.7 (hours), respectively. Although these values were comparable on average to those previously reported, there were noticeable differences with respect to the various time courses of drug plasma concentration among each patient. CONCLUSION: Computations speculated that the trough and peak plasma concentrations as well as the AUC at steady-state change significantly depending on each patient. It suggests that individual pharmacokinetic values of lamivudine should be determined before deciding the optimal administration dose for specific patients.

Adult↗
PubMed1998

Analysis of clinical AIDS-free interval after CD4+ cell counts fall below 200 x 10(6) L-1 in Japanese haemophiliacs infected with HIV-1.

We analysed the time from the date CD4+ cell counts fell below 200 x 10(6) L-1, defined as ti, to the onset of clinical AIDS, according to the 1987 Centers for Disease Control and Prevention case definition, in 129 Japanese haemophilia patients infected with HIV-1. The cumulative onset of clinical AIDS was analysed by the Kaplan-Meier method and proportional hazard model. Incorporated covariates were age of each patient at time ti, as well as CD4+ and CD8+ cell counts, serum levels of IgG, IgA, IgM, GOT and GPT at ti. The time of antiretroviral treatment initiation was also considered. The 50% AIDS-free interval after ti was 3.00 years (95% confidence interval (CI), range 0.49-5.51) and 1.71 years (95% CI, range 0.66-2.76) for the patients at CDC stage II and stage III, respectively (significantly different, P = 0.0013). Among the patients at CDC stage II at ti, higher levels of IgA were tightly associated with a shorter period from ti to onset of clinical AIDS (P < 0.0001), and relative hazard was 1.35 (95% CI, 1.11-1.64) with increase of IgA level by 1.0 g L-1. Thus there is a broad distribution in the time to onset of clinical AIDS in Japanese haemophiliacs even after CD4+ cell counts fall below 200 x 10(6) L-1. This should be taken into consideration in deciding upon the therapy and care of HIV-1 infected people.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Using Gaussian-like input rate function in the two-compartment model. Formulation and application to analysis of didanosine plasma concentration in two Japanese hemophiliacs.

We used a time-dependent input rate function in the two-compartment model to simulate drug plasma concentrations after an oral administration. The input rate term has a Gaussian-like structure with two parameters, time to maximum absorption rate (tm) and measure of the duration of the absorption process (s). This structure corresponds to the scenario in which the absorption rate of the drug into the central compartment changes unimodally with respect to time after administration with a single peak at time tm. We demonstrate the applicability of this formulation in the simulation of plasma concentration of didanosine after oral administration in two Japanese hemophiliacs. We found that we were able to simulate the time courses of the didanosine plasma concentrations in both patients using the theoretical equation with the input term included, and that we were able to determine the six parameters in the equation by the least squares estimation. Pharmacokinetic values derived from the best-fit curve were almost comparable to those reported in other literature except that the Cmax and AUC0-infinity seemed to be slightly higher than those reported elsewhere. Although we are unable to verify the accuracy of this formulation because of the lack of sufficient Japanese data, we are able to demonstrate its efficacy and convenience in the application presented here.

AIDS-Related Complex↗
PubMedDate not supplied

Determination of pharmacokinetic parameters of stavudine in Japanese patients infected with HIV-1, using a Gaussian-like input rate function.

We sought to examine variation in pharmacokinetic parameters of stavudine in Japanese patients infected with HIV-1. Stavudine concentrations were measured in two hemophiliacs (HIV-1 asymptomatic carriers (ACs)) and two non-hemophiliacs (both ACs). To simulate the plasma stavudine concentrations following a single oral dose, we used a Gaussian-like input rate function in a single compartment model. The theoretical equation successfully simulated changes in the time course of plasma stavudine concentrations in all four patients. The mean+/-SD of Tmax, Cmax, AUC0-infinity, and t 1/2 were 0.96+/-0.26 hr, 478+/-90 ng/mL, 1112+/-136 ng x hr/mL, and 1.26+/-0.23 hr, respectively. Pharmacokinetic characteristics were comparable to those reported in the literature, although the mean of Cmax was slightly lower and means of Tmax and t 1/2 slightly longer than those previously reported. Interpatient variability in plasma stavudine concentrations was not as dramatic as that seen with lamivudine. Thus, we confirmed the validity of the uniform therapeutic regimen of stavudine in Japanese people with HIV-1 infection.

Adult↗