In vivo evaluation of guar gum-based colon-targeted drug delivery systems of ornidazole in healthy human volunteers

The aim of the present study was to find the in vivo performance of guar gum-based colon-targeted tablets of ornidazole (dose 250 mg) in comparison with an immediate release tablet of ornidazole (250 mg) in human volunteers. Six healthy volunteers participated in the study, and a cross over design was followed. The plasma concentration of ornidazole was estimated by HPLC. The immediate release tablets of ornidazole produced peak plasma concentration (Cmax of 2171.33+/-278.15 ng/ml) at 2.91+/-0.14 h (Tmax) whereas colon-targeted tablets produced peak plasma concentration (Cmax of 1716.66+/-125.83 ng/ml) at 11.91+/-0.14 h. The delayed Tmax, decreased Cmax, and decreased ka of ornidazole from guar gum-based colon-targeted ornidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in stomach and small intestine, but targeted to colon. Slow absorption of ornidazole from the less absorptive colon might result in the availability of drug for local action in the colon.     

Pharmacokinetic evaluation of guar gum-based colon-targeted oral drug delivery systems of metronidazole in healthy volunteers.

The present study was carried out to find the in vivo performance of guar gum-based colon-targeted tablets of metronidazole as compared to an immediate release tablets in human volunteers. Six healthy volunteers participated in the study and a crossover design was used. Blood samples were obtained at different time intervals and the plasma concentration of metronidazole was estimated by reverse phase HPLC. The immediate release tablets of metronidazole produced peak plasma concentration (Cmax of 2990 +/- 574.6 ng/mL) within 2.8 +/- 0.6 h. On oral administration of colon-targeted tablets, metronidazole started appearing in the plasma between 5 h and 8 h, and reached the peak concentration (Cmax of 1940.0 +/- 528.4 ng/mL) at 11.1 +/- 2.1 h (Tmax). The AUC(0-infinity) and t(1/2) of metronidazole were unaltered on administering the drug as a colon-targeted tablet indicating that the extent of absorption and elimination were not affected by targeting the drug to the colon. However, colon-targeted tablets showed delayed tmax and absorption time (ta), decreased Cmax and decreased absorption rate constant as compared to immediate release tablets. This in turn indicated that metronidazole was delivered to the colon resulting in a slow absorption of the drug and making it available for local action in the colon.     

In Vivo Evaluation of Guar Gum-based Colon-targeted Drug Delivery Systems of Ornidazole in Healthy Human Volunteers

The aim of the present study was to find the in vivo performance of guar gum-based colon-targeted tablets of ornidazole (dose 250 mg) in comparison with an immediate release tablet of ornidazole (250 mg) in human volunteers. Six healthy volunteers participated in the study, and a cross over design was followed. The plasma concentration of ornidazole was estimated by HPLC. The immediate release tablets of ornidazole produced peak plasma concentration (C max of 2171.33 ± 278.15 ng/ml) at 2.91 ± 0.14 h (T max) whereas colon-targeted tablets produced peak plasma concentration (C max of 1716.66 ± 125.83 ng/ml) at 11.91 ± 0.14 h. The delayed T max, decreased C max, and decreased k a of ornidazole from guar gum-based colon-targeted ornidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in stomach and small intestine, but targeted to colon. Slow absorption of ornidazole from the less absorptive colon might result in the availability of drug for local action in the colon.     

In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets

The objective of the present study is to compare the guar gum-based colon-targeted tablets of 5-fluorouracil against an immediate release tablet by in vitro dissolution and in vivo pharmacokinetic studies in human volunteers. Twelve healthy volunteers participated in the study. 5-Fluorouracil was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablet. On oral administration of colon-targeted tablets, 5-fluorouracil started appearing in the plasma at 6 h, and reached the peak concentration (C_max of 216±15 ng/ml) at 7.6±0.1 h (T_max), whereas the immediate release tablets produced peak plasma concentration (C_max of 278±21 ng/ml) at 0.6±0.01 h (T_max). The AUC_0−∞ for 5-fluorouracil from colon-targeted tablet and immediate release tablet were found to be 617±39 and 205±21 ng/ml/h, respectively. Colon-targeted tablets showed delayed t_max, delayed absorption time (t_a), decreased C_max and decreased absorption rate constant when compared to the immediate release tablets.The results of the study indicated that the guar gum-based colon-targeted formulation did not release the drug in stomach and small intestine, but delivered it to the colon resulting in a slow absorption of the drug and making it available for local action in colon.     

Pharmacokinetic evaluation of guar gum-based colon-targeted drug delivery systems of tinidazole in healthy human volunteers

The aim of the present investigation was to determine the in vivo availability of guar gum-based colon-targeted tablets of tinidazole in comparison with immediate release tablets of tinidazole in human volunteers. Six healthy volunteers participated in the study, and a cross-over design was used. The plasma concentration of tinidazole was estimated by HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of tinidazole versus time data. The immediate release tablets of tinidazole produced a peak plasma concentration (C_max of 3239 ± 428 ng/ml) at 1.04 ± 0.32 hr (T_max), whereas colon-targeted tablets produced peak plasma concentration (C_max of 2158 ± 78 ng/ml) at 14.9 ± 1.6 hr. The delayed T_max, decreased C_max, and K_a, and unaltered bioavailability and elimination half-life of tinidazole from guar gum-based colon-targeted tinidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in the stomach and small intestine but delivered to the colon. Slow absorption of the drug from the less absorptive colon might result in the availability of the drug for local action in the colon. The guar gum-based colon-targeted tablets of tinidazole may be useful in providing an effective and safe therapy of intestinal amoebiasis.     

A double-site absorption model fits to pharmacokinetic data of repaglinide in man.

The plasma concentrations of repaglinide in 16 male subjects were determined after an oral dose of 4 mg. Two-peak concentrations in plasma were observed. A type of one-compartment model with double sites of drug absorption was developed and successfully used to fit the data. A good agreement between observed and predicted data was found in all subjects with correlation index r2 > 0.97. The corresponding pharmacokinetic parameters were estimated as follows: Tmax1 0.61 +/- 0.14 h, Tmax2 1.45 +/- 0.43 h, Cmax1 40.60 +/- 20.57 ng/ml, Cmax2 42.70 +/- 17.54 ng/ml, T1 0.12 +/- 0.07 h, T2 0.67 +/- 0.30 h and T3 1.03 +/- 0.35 h.     

Comparative bioavailability of a new formulation of fluoxetine drops.

Fluoxetine drops and marketed fluoxetine capsules had quite the same Cmax (50.25 +/- 4.43 vs 47.55 +/- 5.29 ng/ml), but significantly different AUC0-t (717.27 +/- 71.29 vs 644.91 +/- 78.91 ng/ml/h). Furthermore the drops were characterised by a very early Tmax (4.61 +/- 0.85 hours) with a highly significant difference in comparison to the capsules reference compound (6.72 +/- 1.23 hours). After log transformation 90% C.I. for Cmax, AUC 0-t and AUC0-. were 1.05, 1.11, 0.82 respectively. The two products, therefore, cannot be considered bioequivalent. Our results demonstrate that fluoxetine drops and capsules significantly differ for their pharmacokinetics, with an earlier Tmax and a higher AUC0-t after the administration of the drops preparation.     

Determination of azelnidipine by LC-ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers

A simple, rapid and sensitive high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay for determination of azelnidipine in human plasma using perospirone as the internal standard (IS) was established. After adjustment to a basic pH with sodium hydroxide solution, plasma samples were extracted with diethyl ether and separated on a C18 column with a mobile phase of methanol-5 mM ammonium acetate solution (90:10, v/v). The lower limit of quantification (LLOQ) was 0.20 ng/ml. After administration of a single dose of azelnidipine 8mg and 16 mg, respectively; the area under the plasma concentration versus time curve from time 0 h to 96 h (AUC(0-96) were (186 +/- 47) ng ml(-1) h, (429 +/- 145) ng ml(-1) h, respectively; clearance rate (CL/F) were (45.94 +/- 11.61), (42.11 +/- 14.23) L/h, respectively; peak plasma concentration Cmax were (8.66 +/- 1.15), (19.17 +/- 4.13) ng/ml, respectively; apparent volume of distribution (Vd) were (1749 +/- 964), (2480 +/- 2212) L, respectively; time to Cmax (Tmax) were (2.8 +/- 1.2), (3.0 +/- 0.9) h, respectively; elimination half-life (t(1/2beta)) were (22.8 +/- 2.4), (23.5 +/- 4.2) h, respectively; and MRT were (25.7 +/- 1.3), (26.2 +/- 2.2) h, respectively; The essential pharmacokinetic parameters after oral multiple doses (8 mg, q.d.) were as follows: (Cmax) ss, (15.04 +/- 2.27) ng/ml; (Tmax) ss, (2.38 +/- 0.92) h; (Cmin) ss, (3.83 +/- 0.94) ng/ml; C(av), (7.05 +/- 1.54) ng/ml; DF, (1.62 +/- 0.26); AUCss, (169.19 +/- 36.87) ng ml(-1) h.     

Development of a HPLC-UV assay for silybin-phosphatidylcholine complex (silybinin capsules) and its pharmacokinetic study in healthy male Chinese volunteers.

To develop a new HPLC-UV method of determining silybin in human plasma and to study the pharmacokinetic of silybin-phosphatidylcholine complex (silybinin capsules) in healthy male Chinese volunteers using the new developed method. The assays were validated over the concentration range of 3.5-14336.0 ng x ml(-1) in human plasma. In either matrix, the lower limit of quantitation was 3.5 ng x ml(-1). The intra- and inter-day precision were less than 10% in terms of RSD. The absolute recovery was more than 90%. The validated assay was suitable for pharmacokinetic studies of silybin. In order to assess its pharmacokinetic profile in human, plasma silybin levels were determined after administration of single oral doses of silybin-phosphatidylcholine complex (equivalent to 280 mg silybin) to 20 subjects. Silybin was absorbed rapidly, the times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67 h, and the mean was 1.4 h. Other Pharmacokinetic parameters of silybin in human were Cmax 4242.1 +/- 2252.9 ng x ml(-1); AUC(0-infinity) 5946.6 +/- 1898.9 ng x h x ml(-1); K(el) 0.31 +/- 0.08 h(-1); t1/2 2.38 +/- 0.76 h; Ka 5.48 +/- 2.00 h(-1); CL 55.0 +/- 28.1 L x h(-1); Vd 191.7 +/- 125.1 L, respectively.     

Similar bioavailability of dexmethylphenidate extended (bimodal) release, dexmethyl-phenidate immediate release and racemic methylphenidate extended (bimodal) release formulations in man

OBJECTIVE: The d-isomer of methylphenidate (d-MPH) is the pharmacologically active part of the racemic mixture of methylphenidate (d,l-MPH), which has been used for decades in the treatment of attention-deficit/hyperactivity disorder (ADHD). A modified release formulation with bimodal release for the pure d-enantiomer (Focalin XR) has been developed to enable a fast onset of action and a sustained activity for once-daily administration. It was intended to achieve a bimodal concentration-time profile as observed after administration of two immediate release Focalin tablets. The pharmacokinetics of this d-MPH bimodal release formulation were compared with a d-MPH immediate release formulation and a similar bimodal release formulation of d,l-MPH in healthy adult volunteers. MATERIALS AND METHODS: 25 volunteers received a single 20 mg dose of d-MPH bimodal release formulation, two 10 mg doses of a d-MPH immediate release formulation given 4 h apart and a single 40 mg dose of d,l-MPH bimodal release formulation (1 : 1 ratio for d : l enantiomers). The washout between treatments in this 3-way crossover study was 7 days. RESULTS: All three formulations were well-tolerated at the doses tested. The d-MPH bimodal release formulation generated two distinct d-MPH plasma concentration peaks and both peak concentrations and the time to peak were similar to those of the d-MPH immediate release formulation given 4 h apart and the d,l-MPH bimodal release formulation. The three formulations had Cmax and AUC0-infinity values of 15.5 +/- 4.3 ng/ml and 119 +/- 41 ng x h/ml for bimodal release d-MPH, 17.9 +/- 5.3 ng/ml and 115 +/- 40 ng A h/ml for immediate release d-MPH, and 16.4 +/- 4.4 ng/ml and 122 +/- 36 ng x h/ml for d,l-MPH bimodal release, respectively. CONCLUSIONS: In summary, the 20 mg extended (bimodal) release formulation of d-MPH (Focalin XR) demonstrated a bimodal concentration-time profile and was bioequivalent to two 10 mg doses of immediate release d-MPH (Focalin) and was bioequivalent to 40 mg extended (bimodal) release d,l-MPH (Ritalin LA).     

Nasal mucoadhesive delivery systems of the anti-parkinsonian drug, apomorphine: influence of drug-loading on in vitro and in vivo release in rabbits.

Lyophilized polyacrylic acid powder formulations loaded with apomorphine HCl were prepared and the influence of drug loading on in vitro release and in vivo absorption studied after intranasal administration in rabbits. These formulations prepared with Carbopol 971P, Carbopol 974P and polycarbophil sustained apomorphine release both in vitro and in vivo. The in vitro release rate and mechanism were both influenced by the drug loading. There was no large influence of drug loading on the time to achieve the peak (Tmax) for a particular polymer, but Tmax differed between different polymers. For a particular drug loading, the Tmax from Carbopol 971P was the slowest compared with that for Carbopol 974P and polycarbophil; however, only the Tmax from Carbopol 971P loaded with 15% w/w of apomorphine was significantly longer than polycarbophil of similar drug loading (P=0.0386). The trend further observed was that increasing drug loading led to increased peak plasma concentration and area under the curve (AUC). In the second part of this study, a mixture containing an immediate release component and sustained release formulation was administered in an attempt to increase the initial plasma level, as this could be therapeutically beneficial. Only one peak plasma concentration was observed and the initial plasma concentrations were no higher than those obtained with solely sustained release formulation. The Tmax, the peak plasma drug concentration (Cmax) and AUC from the lactose-containing formulation were lower than the formulation without lactose but the differences were only marginally statistically significant for Cmax (P=0.0911) and AUC (P=0.0668), but not Tmax (P=0.2788).     

In vitro and in vivo evaluation of guar gum-based matrix tablets of rofecoxib for colonic drug delivery

The present study was carried out to develop and evaluate guar gum-based matrix tablets of rofecoxib for their intended use in the chemoprevention of colorectal cancer. Matrix tablets containing 40% (RXL-40), 50% (RXL-50), 60% (RXL-60) or 70% (RXL-70) of guar gum were prepared by wet granulation technique, and were subjected to in vitro drug release studies. Guar gum matrix tablets released only 5 to 12% of rofecoxib in the physiological environment of stomach and small intestine. The matrix tablets RXL-40 disintegrated completely within 10 h in a dissolution medium without rat caecal contents (control study), and hence not studied further. When the dissolution study was continued in simulated colonic fluids (rat caecal content medium), the matrix tablets RXL-50 were acted upon by colonic bacterial enzymes releasing the entire quantity of drug wherein there was no appreciable difference when compared to that released in control study. The matrix tablets RXL-60 released another 88% of rofecoxib whereas matrix tablets RXL-70 released only 57% of rofecoxib in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The guar gum matrix tablets RXL-70 were subjected to in vivo evaluation in human volunteers to find their ability of targeting rofecoxib to colon. The delayed Tmax, prolonged absorption time (ta), decreased Cmax and decreased ka indicated that rofecoxib was not released significantly in stomach and small intestine, but was delivered to colon resulting in a slow absorption of the drug and making it available for local action in human colon.     

The pharmacokinetics of captopril in infants with congestive heart failure

The use of the angiotensin-converting enzyme inhibitor captopril in infants with congestive heart failure (CHF) has been empirical owing to a lack of relevant pharmacokinetic data. To determine standard pharmacokinetic parameters for the drug in this population, we administered captopril, 1 mg/kg, orally to 10 infants aged 6.8 +/- 4.6 months. Sequential plasma unchanged and total (sum of unchanged and dimerized) captopril concentrations were determined using a high-performance liquid chromatographic method. Arterial pressure, systemic and pulmonary resistance, heart rate, and respiratory rate were all significantly decreased 1 h after the first dose of captopril. Plasma renin activity was not significantly increased. For unchanged captopril, the maximum concentration (Cmax) was 350 +/- 184 ng/ml; the time to Cmax (Tmax), 1.6 +/- 0.4 h; elimination half-life (t1/2), 3.3 +/- 3.3 h; oral clearance (Clo), 1.1 +/- 0.4 L/h/kg. For total captopril, Cmax was 1,088 +/- 621 ng/ml; Tmax, 2.7 +/- 1.1 h; t1/2, 3.4 +/- 1.0 h. Thus, we conclude that the pharmacokinetic parameters for captopril in infants with CHF are within the range reported for adults with CHF. Also, the hemodynamic changes, measured 1 h after the first dose, indicate that the acute effects of captopril in infants with CHF are beneficial.     

自制甲硝唑缓释微球结肠溶胶囊在家兔体内药代动力学研究

目的研究甲硝唑缓释微球结肠溶胶囊在家免体内的药代动力学,评价其在结肠的释放及吸收特性。方法选取家兔作为受试动物,双周期交叉设计,采用高效液相色谱法测定家兔静脉血中的甲硝唑浓度,计算药代动力学参数。结果实验组：ke0．259／h,tl／22．679h,Tmax8．5h,Cmax4．617μg／ml,AUC25．279μg·h／ml;对照组：ke0．325／h,t1／2 2．133h,Tmax1h,Cmax13．499μg／ml,AUC49．889μg·h／ml;实验组相对生物利用度为50．7％。结论甲硝唑微球结肠溶胶囊在结肠内缓慢释放,降低了血药浓度。     

LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsule in human volunteers

The purpose of the present study was to develop a standard protocol for loperamide hydrochloride bioequivalence testing. For this purpose, a simple rapid and selective LC-MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of loperamide hydrochloride in human plasma, and we followed this with a bioavailability study. Methyl tert-butylether (MTBE) was used to extract loperamide hydrochloride and ketoconazole (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a Zorbax RX C18 column (5 microm, 2.1 mm x 150 mm) using acetonitrile-water-formic acid (50:50:0.1 (v/v)) as a mobile phase. The retention times of loperamide hydrochloride and IS were 1.2 and 0.8 min, respectively. Quadrupole MS detection was by monitoring at m/z 477 (M + 1) corresponding to loperamide hydrochloride and at m/z 531 (M + 1) for IS. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of loperamide hydrochloride was evaluated in eight healthy male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of four 2mg capsules of loperamide: the area under the plasma concentration versus time curve from time 0 to 72 h (AUC72 h) 19.26 +/- 7.79 ng h/ml; peak plasma concentration (Cmax) 1.18 +/- 0.37 ng/ml; time to Cmax (Tmax) 5.38 +/- 0.74 h; and elimination half-life (t1/2) 11.35 +/- 2.06 h. The developed method was successfully used to study the bioavailability of a low dose (8 mg) of loperamide hydrochloride.     

盐酸曲马多缓释滴丸兔体内药动学研究

目的：比较盐酸曲马多缓释滴丸与普通片剂在兔体内的药代动力学和生物利用度。方法：以普通片为对照,采用高效液相色谱法测定兔体内的血药浓度。结果：缓释滴丸和普通片的药-时曲线下面积分别为（6 567.71±231.69）ng/ml.h和（5 954.87±93.85）ng/ml.h;缓释滴丸的Cmax、Tmax分别为542 ng/ml和5.25 h;普通片分别为953 ng/ml和2h。结论：缓释滴丸比普通片能持久维持平稳的血药浓度,增强了用药的有效性和安全性。     

In vitro evaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D-coated colon-targeted pellets of indomethacin

A pH- and enzyme-dependent colon-targeted multi-unit delivery system of indomethacin was developed by coating guar gum and Eudragit FS30D sequentially onto drug-loaded pellets in a fluidized bed coater. In vitro studies showed that smaller coating weight gain of guar gum resulted in reduced release lag time t10 (10% release time), but favored degradation by enzymes (galactomannanase). A cumulative weight gain (CWG) of 44% provided sufficient enzymatic sensitivity and protection of the core. Under gradient pH conditions (pH = 1.2, 6.8, 7.4 and 6.5 for 2, 2, 1 and 15 h, respectively), indomethacin was released from Eudragit FS30D-coated pellets quickly after changing pH to 7.4. For guar gum/Eudragit FS30D double-coated pellets, only about 5% of the drug was released after another 1 h, showing retarding effect by guar gum coating. After changing pH to 6.5 and addition of galactomannanase, enzyme-dependent drug release was observed. Pharmacokinetic study in beagle dogs showed that fastest absorption with the smallest Tmax and Tlag was observed for uncoated pellets. The Tmax and Tlag of Eudragit FS30D-coated pellets were postponed to about 2.5 and 1 h, respectively. After a further guar gum coating, Tlag was further postponed to about 2.8 h, about 2 h of additional lag time on the basis of Eudragit FS30D coating. It is indicated that the guar gum/Eudragit FS30D-coated system has potential to be used to deliver drugs to the colon.     

抵克力得胶囊及片剂的药动学研究

8名健康男性志愿者，随机交叉口服抵克力得胶囊与片剂，反相HPLC测定其血药浓度，运用PKBPN1软件处理数据。结果，国产胶囊和进口片剂的动力学参数已。Cmax分别为1832．62±673．47ng／ml，1593．11±354．06ng／ml；Tmax为2．3，2．5h；Ka为1．47h－，1．56h-，（T1／2）β12．07，10．72h；AUC_（0→∞）11548．01ng·h／L，12611．67ng·h。两制剂的药动学参数无统计学差异。     

Pharmacokinetic profile and bioavailability of a new pharmaceutical formulation of isosorbide-5-mononitrate sustained-release formulation

The pharmacokinetic profile and the bioavailability of a new galenic formulation of isosorbide-5-mononitrate sustained released capsules (Olicard 40 retard) was tested under standardized conditions. 12 healthy, male volunteers (mean age 24.9 +/- 3.0 years) in a randomized, intraindividual crossover design (wash-out phase: 6 days) received the isosorbide-5-mononitrate sustained-release capsules (testformulation) and a standard-release formulation of the same active substance as single dose (40 mg each). Venous blood sampling for analysing the plasma concentration of isosorbide-5-mononitrate was done before and at 21 fixed times after medication. The AUC0----36h of the concentration/time curve was calculated using the linear trapezoidal rule and the AUC0----infinity extrapolated after computing the half-life of the terminal elimination phase. The leading variable was the AUC0----infinity. For the sustained-release preparation an AUC0----36h of 5764.5 +/- 909 ng/ml.h was measured, an AUC0----infinity of 5863.9 +/- 981.9 ng/ml.h was calculated, with a peak maximum (Cmax) of 472.5 +/- 29.7 ng/ml after 2.9 +/- 0.5 h (tmax). For the standard-release formulation an AUC0----36h of 5679.8 +/- 690.3 ng/ml.h was measured, an AUC0----infinity of 5688.7 +/- 695.7 ng/ml.h was calculated, with a peak maximum (Cmax) of 842.4 +/- 100.2 ng/ml after 1.2 +/- 0.2 h (tmax). The bioavailability of the standard-release formulation was postulated to be 100%. The non-parametric calculation of the bioavailability-ratio (geometric Walsh-averages) was 101.47% (95% confidence limits 85.24% to 121.09%). There was no statistically significant difference between the both galenical formulations, the sustained-release preparation has no influence on the total amount of resorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.