The bioavailability of doxycycline

The bioavailability of doxycycline (Doxy-Diolan 100 tablets, test, active substances: 100 mg doxycyclin per tablet) was compared with that of another commercially available tablet-formulation containing the same active substance (reference). In a cross-over study, 16 young healthy male volunteers were administered in fasting state orally by one tablet containing 100 mg active substance. The concentrations of doxycycline were determined in plasma and saliva by a high-performance liquid chromatographic assay. Mean maximum plasma concentration (cmax +/- standard deviation) of doxycycline were 1.57 +/- 0.40 micrograms/ml (test) and 1.59 +/- 0.38 micrograms/ml (reference), respectively, and were reached 1.47 +/- 0.55 h and 1.66 +/- 0.57 h after administration. Plasma half-lives were 16.6 +/- 2.9 h and 16.8 +/- 3.0 h, the areas under the plasma concentration-time curves (AUC0-00) 29.3 +/- 4.5 mg/l.h and 29.7 +/- 4.4 mg/l.h. The concentration of doxycycline in saliva were low, median maximum concentrations of 50 ng/ml were measured 1-2 h after administration. The statistical evaluation revealed bioequivalence between both drugs.     

Relative bioavailability of three cefixime formulations

Three galenic formulations of cefixime (tablet, syrup and dry suspension) containing 200 mg each were compared with respect to their relative bioavailability in twelve healthy volunteers. All three formulations showed reliable absorption. Mean peak plasma concentrations were reached after 3.3-3.5 h, mean terminal half lives were 2.9-3.1 h. 18-24% of the dose administered were recovered unchanged in the urine. Best bioavailability was obtained with the dry suspension (AUC0-infinity = 25.8 +/- 7.0 micrograms/ml h; Cmax = 3.4 +/- 0.9 microgram/ml), followed by the tablet (AUC0-infinity = 20.9 +/- 8.1 micrograms/ml h; Cmax = 3.0 +/- 1.0 micrograms/ml) and the syrup which is based on triglycerides (AUC0-infinity = 17.8 +/- 5.9 micrograms/ml h; Cmax = 2.4 +/- 0.7 micrograms/ml). The statistical analysis resulted in bioinequivalence between dry suspension and syrup. It is concluded that best bioavailability of cefixime after oral administration is guaranteed when taken in an "aqueous medium" either as dry suspension or as tablet with "plenty of liquid".     

罗红霉素片剂生物利用度的比较研究

为比较不同剂型罗红霉素的生物利用度,用微生物管碟检定法(藤黄微球菌CMCC(B)28001)测定了10名男性健康受试者口服罗红霉素分散片(制剂A)和罗红霉素片(制剂B)后不同时间血浆中活性药物的浓度,绘制了血药浓度—时间曲线。结果表明,受试者交叉口服含罗红霉素150mg的制剂A和制剂B后,血浆T_max分别为1.7±0.9和3.7±1.6h,C_max分别为4.97±1.17和2.04±1.26μg·ml^-1,AUC_0→∞分别为62.2±11.9和35.0±16.9μg·h·ml^-1。以制剂A为参比,制剂B中罗红霉素的相对生物利用度仅为59.8%±32.6%,两种制剂的药物吸收程度有显著差异(P<0.01)。初步分析提示,罗红霉素在胃中的迅速溶出是保证其片剂生物利用度的关键之一。     

Bioavailability of quinidine in slow-release form. A comparison between two preparations containing quinidine bisulphate as the active constituent.

Two different slow-release preparations of quinidine bisulphate (A and B) have been tested. The in vitro dissolution rate of preparation B was substantially lower in intestinal than in gastric juice, whereas the release rate of quinidine from preparation A was virtually unaffected by the pH of the dissolution medium. After a single dose of two tablets of each of the preparations to 6 healthy volunteers, corresponding to 386 mg (B) and 320 mg of quinidine base (A), the maximum plasma concentration was attained after about 4.5 h. The peak concentration was 5.2 +/- 0.5 mumol/l for preparation A and 4.1 +/- 0.4 mumol/l for B. A similar difference was found in the area under the plasma concentration curve (AUC), which was 68 +/- 10 mumol-h/l and 54 +/- 5 mumol-h/l, respectively. Taking into consideration that preparation B contained 20.6% more active drug per tablet these values indicate that the extent of bioavailability is about 50% higher for tablet A than for tablet B.     

Salbutamol disposition and dynamics in conscious rabbits: influence of the route of administration and of the dose.

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 micrograms/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 micrograms/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 micrograms/kg), total plasma clearance was 82 +/- 5 ml/min per kg, apparent volume of distribution was 5.0 +/- 0.5 l/kg, and terminal half-life was 41 +/- 2 min. Similar values were estimated when 120 micrograms/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80 +/- 0.19, 0.48 +/- 0.22, and 0.78 +/- 0.46 mmol/l, and for the second group, maximal decrement was 1.31 +/- 0.37, 0.70 +/- 0.24, and 0.84 +/- 0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po > it > iv.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative bioavailability and pharmacokinetics: a combination of pentazocine and acetaminophen

The relative bioavailability and pharmacokinetics of a combination product containing pentazocine and acetaminophen were studied in 20 healthy human males. Each subject, in a single-dose three-way crossover design, received two different preparations containing 50 mg of pentazocine (as base) and 1300 mg of acetaminophen either as capsule-shaped tablets or as a solution. Plasma concentrations of pentazocine and acetaminophen were determined from 0.25 to 12 h following oral administration. The plasma data for both compounds in the tablet formulation were described by an open one-compartment body model with first-order absorption. The average (+/- SD) bioavailability of the tablet relative to that of the solution was 85.0 +/- 31.1 and 88.6 +/- 13.1% for pentazocine and acetaminophen, respectively. The apparent first-order regression-dependent elimination rate constants for pentazocine from the tablet and solution preparations were 0.19 +/- 0.08 and 0.20 +/- 0.06 h-1, respectively, while the rate constants for acetaminophen were 0.26 +/- 0.03 and 0.25 +/- 0.03 h-1 for the tablet and solution preparations, respectively. These rate constants correspond to terminal elimination half-lives of approximately 3.6 h for pentazocine and approximately 2.7 h for acetaminophen.     

Evaluation of the absorption from three ibuprofen formulations

The pharmacokinetic differences between two sustained-release 300 mg (A) and 400 mg (B) formulations and a rapid-release 400 mg ibuprofen conventional sugar-coated formulation (C) were compared after a single dose. Mean peak levels of 25.1 micrograms/ml for preparation A (2 X 300 mg), 31.3 micrograms/ml for preparation B (2 X 400 mg) and 68.5 micrograms/ml for preparation C (2 X 400 mg) were reached at 5.3, 3 and 2 hours respectively, after ingestion of the drugs. The individual plasma-level time-profiles for the majority of doses suggested prolonged absorption of product A and B. The absorption from formulations A and B was significantly slower (p less than 0.001 and p less than 0.05 respectively) than that from the conventional tablets. The bioavailability of ibuprofen from sustained-release capsules, was not found to differ significantly from that of ibuprofen from conventional tablets. The relative bioavailability was very close to 100% in almost all subjects (coefficient of variation 14% and 17%). Projections of plasma concentrations upon multiple dosing were made from single dose data. The dosage interval concentration ratio which reflects both the frequency and the entry of the drug into and from the body was much lower for sustained-release formulations (A: 3.0; B: 3.7; C: 12.9).     

Formulation and in vitro/in vivo investigation of carbamazepine controlled-release matrix tablets

Carbamazepine controlled-release tablet formulations containing hydroxypropyl methylcellulose (HPMC) as matrix material at different concentrations were developed and evaluated in vitro and in vivo. The formulation containing 10% HPMC (HPMC-10) showed a controlled-release profile comparable to that of a commercially available, controlled-release carbamazepine preparation (Tegretol CR 200). The kinetics of controlled-release carbamazepine tablets was examined in eight healthy volunteers. The peak plasma concentration of 1.99 +/- 0.56 micrograms.ml-1 was obtained for HPMC-10 at 15.0 +/- 9.0 h, and 1.33 +/- 0.35 micrograms.ml-1 for Tegretol CR 200 at 15.2 +/- 8.9 h, and AUC0-infinity values of 85.2 +/- 30.8 micrograms.h.ml-1 and 76.9 +/- 20.7 micrograms.h.ml-1, respectively. Developed formulation (HPMC-10) was found to be bioequivalent to Tegretol CR 200 and, controlled release was obtained with smoother concentration-time curve resulting in less fluctuations.     

Single dose bioavailability of two different digoxin tablets

In a single dose bioequivalence study in 10 healthy young adults the absorption profiles and bioavailability of two digoxin containing tablets (A = digoxin-Pharbita 0.25 mg and reference drug B) were compared and related to the in vitro dissolution rate of both tablets. Two tablets of each product (= 0.50 mg of digoxin) were taken at random on an empty stomach; two weeks elapsed between the two treatments. Frequent blood sampling was performed up to 24 h after intake of the dose. Digoxin plasma concentrations were measured by means of radioimmunoassay. No significant differences (p greater than 0.05) were found in the mean values of the peak plasma concentration (cmax), time to peak (tmax) and area under the plasma concentration versus time curve for the period of 0-10 h after drug intake (AUC0-10), although in most subjects the absorption process after intake of product A was slightly faster, with slightly higher peak. This might be related to a slightly faster release of digoxin from the product A dosage form, as was seen from the dissolution test data. The relative bioavailability of product A as compared to product B, accounted for 97.7 +/- 28.7% (mean +/- S.D.). These results indicate, that both products can be considered as being bioequivalent.     

Absolute bioavailability of moxonidine

In a randomized 2-way cross-over study with eighteen healthy male volunteers, two moxonidine preparations (tablets, treatment A vs. intravenous solution, treatment B) were tested to investigate absolute bioavailability and pharmacokinetics of moxonidine. The preparations were administered as single doses of 0.2 mg; prior to and up to 24 h after administration blood samples were collected and the plasma moxonidine concentrations determined. Urine samples were collected prior to and at scheduled intervals up to 24 h after administration for the determination of unchanged moxonidine. Moxonidine plasma and urine concentrations were determined by a validated gas chromatographic/mass spectrometric method with negative ion chemical ionization. The mean areas under the plasma concentration/time curves were calculated as [mean +/- standard deviation] 3438 +/- 962 pg.h/ml (AUC(0----Tlast)) and 3674 +/- 1009 pg.h/ml (AUC(0----infinity)) for treatment A; 3855 +/- 1157 pg.h/ml (AUC(0----Tlast)) and 4198 +/- 1205 pg.h/ml (AUC(0----infinity)) for treatment B. Mean peak plasma concentrations of 1495 +/- 646 pg/ml were attained at 0.56 +/- 0.28 h after oral treatment, mean peak plasma concentrations after intravenous treatment reached 3965 +/- 1342 pg/ml at 0.17 +/- 0.01 h (= coinciding with end of infusion). The mean terminal half-lives of moxonidine were derived as 1.98 h after administration of the tablet and as 2.18 h after infusion. The amounts of moxonidine excreted in urine during the 24 h following administration (Ae(24h)) in absolute figures and as percentage of the dose administered were 102 +/- 26 micrograms or 51 +/- 13% for the tablet and 122 +/- 33 micrograms or 61 +/- 16% for the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioavailability assessment of salbutamol sulfate suppositories in human volunteers

The purpose of this investigation was to evaluate the bioavailability of three salbutamol sulfate suppository formulations. The formulations were; 2 mg salbutamol sulfate in Suppocire NA base containing 6% Eudispert gel (F1), 2mg salbutamol sulfate in Witepsol H15 base containing 3% methyl cellulose gel (F2), and 2 mg salbutamol sulfate in Witepsol W25 base containing 3% methyl cellulose gel (F3). The formulations were administered via rectal route in six healthy male adult volunteers. The bioavailability of the three suppository formulations was compared with the oral bioavailability of salbutamol sulfate 2mg tablets (F4). Six volunteers participated in a four-way crossover study, where each study was separated from the other by an interval of 1 weak. Venous blood samples of 5 ml were taken immediately before dosing and after predetermined time intervals of 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 and 8 h. The result showed that Cmax +/- S.D. observed were 12.96 +/- 2.11, 14.78 +/- 2.33, 10.02 +/- 1.42 and 11.51 +/- 1.22 ng ml(-1) for F1, F2, F3 and F4, respectively. The Tmax +/- S.D. were found to be 1.91 +/- 0.20, 1.83 +/- 0.26, 2.50 +/- 0.00 and 2.67 +/- 0.24 h for F1, F2, F3 and F4, respectively. AUC +/- S.D. values were 40.25 +/- 1.88, 42.16 +/- 1.55, 28.62 +/- 1.98 and 37.63 +/- 1.44 ng h per ml for F1, F2, F3 and F4, respectively. The relative bioavailabilities of the investigated formulations were 112.04, 106.96 and 76.06 for formula F2, F1 and F3, respectively, when compared with the oral preparation (F4). The finding indicates that the bioavailability of salbutamol sulfate can be enhanced by delivering it rectally with Suppocire NA base containing 6% Eudispert gel or with Witepsol W25 base containing 3% methyl cellulose to match that of oral tablets. Salbutamol sulfate can be rectally administered in patients who are less compliant with the oral administration.     

Relative bioavailability of a commercial trifluoperazine tablet formulation using a radioimmunoassay technique

The relative bioavailability of a new conventional tablet formulation (5 mg) of trifluoperazine dihydrochloride was studied in 24 healthy volunteers. Using a sensitive radioimmunoassay technique, plasma trifluoperazine concentrations were measured up until 24 h following ingestion of single 5-mg doses of trifluoperazine. The mean +/- SD for the peak concentration (Cmax), time to Cmax, area under the curve from 0 to 24 h (AUC240), and terminal elimination half-life following the administration of the test formulation were 2.15 +/- 1.07 ng/mL, 4.10 +/- 1.38 h, 21.04 +/- 11.92 ng X h/mL, and 9.5 +/- 7 h, respectively. Following the ingestion of the original trifluoperazine tablet formulation (5 mg) these same parameters were estimated to be 1.92 +/- 0.88 ng/mL, 4.02 +/- 1.10 h, 18.03 +/- 10.11 ng X h/mL, and 9.3 +/- 7 h, respectively. Large intersubject variations in Cmax and AUC240 were observed. The relative bioavailability of the test formulation was calculated to be 106.5 +/- 25.5%.     

Relative bioavailability of two spray formulations of nitroglycerin

Twelve healthy male volunteers received two sublingual doses of 0.4-mg nitroglycerin from two metered-dose spray products, A and B. Plasma samples were collected immediately before and for up to 6 h following each dose. The samples were immediately extracted and analyzed for nitroglycerin. The results show striking differences between the two formulations. The mean AUC for preparation A, 159 +/- 66 h X pg/mL, was 2.7 times greater than for B, 59 +/- 33 h X pg/mL. The mean maximum plasma concentration for A was 1387 +/- 620 pg/mL which was 4.1 times greater than the mean maximum plasma concentration for preparation B (340 +/- 234 pg/mL). The time of maximum plasma concentration also occurred earlier for preparation A versus B, 4.3 +/- 1.6 versus 8.3 +/- 2.0 min, respectively. Such bioavailability differences may indicate therapeutic advantages for preparation A.     

Comparative biological availability of two different ibuprofen granules]

Bioavailability of ibuprofen (CAS 15687-27-1) was investigated in 12 healthy volunteers who received 2 sachets of newly developed effervescent granules (Imbun), each containing 500 mg of ibuprofen lysine salt (corresponding to 292.6 mg of ibuprofen) as the test preparation and 1 sachet of commercially available granules containing 600 mg ibuprofen. Blood samples were withdrawn pre-dose and at 16 occasions until 10 h post dose. Ibuprofen plasma concentrations were assayed by HPLC using a proprietary column-switching technique. Maximum plasma concentrations, Cmax, and times of their occurrence, tmax, were taken from the plasma data directly, areas under the plasma level/time curves, AUC0-10, were calculated using the trapezoidal rule. Pharmacokinetic parameters were checked for significant differences using ANOVA with p = 0.05. When the test preparation was applied maximum ibuprofen levels of 60 +/- 17 micrograms/ml were reached at 27 +/- 17 min p. appl. while Cmax was 52 +/- 12 micrograms/ml at tmax = 94 +/- 27 min after application of the reference preparation. AUC values were 150 +/- 44 microgramsh/ml (test) and 148 +/- 33 microgramsh/ml (reference), respectively. Thus, relative bioavailability of ibuprofen was 101.8 +/- 16.3% (or 104.1 +/- 16.7% when the slight differences in doses were corrected for). Differences in extent of absorption as measured by AUC and Cmax proved to be insignificant whereas differences in absorption rate as measured by tmax were highly significant (p < 0.001).     

硫酸沙丁胺醇口腔崩解片人体生物等效性研究

目的 :比较硫酸沙丁胺醇口腔崩解片和普通片的人体生物利用度。方法 :18名健康志愿受试者随机交叉单剂口服硫酸沙丁胺醇口腔崩解片和普通片 ,用高效液相色谱法测定血药浓度 ,以3p97程序计算药动学参数和生物利用度。结果 :硫酸沙丁胺醇口腔崩解片和普通片体内药 -时曲线符合二室模型 ,崩解片和普通片Cmax 分别为 (17 65±6 48)ng/ml和 (16 60±6 21)ng/ml,Tmax 分别为 (1 92±1 18)h和 (2 03±1 17)h ,AUC0～24 分别为 (127 23±32 41)ng/(h·ml)和 (131 42±37 73)ng/(h·ml) ,相对生物利用度为 (99 32±15 58) %。结论 :硫酸沙丁胺醇口腔崩解片与普通片具有生物等效性     

Pharmacokinetic modelling of the plasma concentration-time profile of the vitamin retinyl palmitate following intramuscular administration

Seven healthy male volunteers (21-24 y) received by the ventro-gluteal route a single dose of 100,000 I.U. of the vitamin retinyl palmitate (RP) in a water-miscible preparation (W) and 5 weeks later the same dose in an oily solution (S). After administration of W median (range) peak plasma concentrations of 5.6 (4.4-8.7). 10(3) micrograms l-1 were reached after 12 h and high levels persisted for another 50 h. At 144 h levels were still, by a factor 3, higher than baseline. Plasma levels of RP after S remained close to baseline (20-50 micrograms.l-1) suggesting negligibly low bioavailability. The plasma level profile of RP after W could well be described by use of a one-compartment model with Weibull-type absorption and Michaelis-Menten elimination. The median (range) absolute bio-availability (estimates of lower limits) was 42 (32-52) per cent.     

Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs

The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg po of ketoconazole as tablet (Ktab) and solution (Ksol) formulations. The dogs received 400 mg po of Ktab and Ksol, and 376 mg iv of an intravenous dose (Kiv). In humans the AUC value for Ksol (62.21 +/- 21.2 microgram X h/ml; mean +/- SD) was significantly greater than for Ktab (50.0 +/- 15.2 micrograms X h/ml; p less than 0.05). Peak serum concentrations (Cmax), time to peak serum concentrations (tmax), t1/2, and the terminal elimination rate constant (kel) did not differ between Ktab and Ksol. This suggests that the administration of Ksol may be a useful alternative to dosage increases in situations where low bioavailability of ketoconazole in tablet form is suspected. The mean systemic clearance (CLs) of Kiv in dogs was 2.74 +/- 1.10 mL/min/kg, the volume of distribution at steady state (Vdss) was 0.72 +/- 0.28 L/kg, and the half-life was 2.7 +/- 1.6 h. Considerable variability was seen in the AUC of ketoconazole, particularly with the oral preparations. The absolute bioavailability of Ktab was 0.50 +/- 0.38, which did not differ statistically from that of Ksol, 0.56 +/- 0.23. The Ksol showed less variability in AUC, Cmax, and F values than did Ktab, and two dogs with low bioavailability with Ktab (0.04 and 0.07) had substantially greater bioavailability with Ksol (F = 0.96 and 0.57, respectively). Evaluation of Kiv in dogs confirms decreased bioavailability from orally administered tablet formulations of ketoconazole.     

沙丁胺醇气雾剂在健康受试者体内的药物动力学和相对生物利用度

目的:研究沙丁胺醇气雾剂在健康受试者的药物动力学和生物利用度.方法:十名健康男性志愿者单剂量吸入1.2 mg沙丁胺醇气雾剂或口服沙丁胺醇水溶液.用HPLC法测定人血浆中沙丁胺醇浓度.以非房室模型计算药物动力学参数,计算气雾剂相对水溶液的生物利用度.结果:气雾剂和口服溶液的药物动力学参数如下:T_(max)(0.22±0.07)和(1.8±0.6)h,C_(max)(3.4±1.1)和(3.9±1.4)μg·L~(-1),T_(1/2)(4.5±1.5)和(4.6±1.1)h,AUC_(0-20min)(0.9±0.3)和(0.16±0.10)μg·h·L~(-1).两种给药途径的T_(max)和AUC_(0-20 min)之间差异显著(P<0.01).AUC_(0-20min)(nihal)为 AUC_(0-20 min)(po)的 8倍.沙丁胺醇气雾剂相对口服溶液的生物利用度为 57％±24％.结论:沙丁胺醇气雾剂在人体的吸收过程与口服溶液差异有显著性.     

The relative bioavailability of co-trimoxazole suspensions

The relative bioavailability of a co-trimoxazole suspension manufactured by VEB Berlin-Chemie (B); Belocid-Suspension was compared with a widespread used suspension (V) in healthy male students (22-29 ys. aged). A single oral dose of 160 mg trimethoprim (TPM) and 800 mg sulphamethoxazole (SMZ) produced similar blood levels with either preparation. The TMP peak levels were 1.44 +/- 0.18 (B) and 1.40 +/- 0.26 mg/l (V), respectively after 1.5 and 1.0 h on an average. The AUC amounted to 18.94 +/- 2.25 (B) and 17.19 +/- 3.62 mg . h/l (V), respectively. About one half (52.5%) of the given TMP dose was excreted unchanged by kidney within 48 h after administration of the respective suspension. The SMZ peak levels run to 37.2 +/- 10.3 (B) and 38.6 +/- 5.4 mg/l (V) after 3.6 +/- 3.5 and 1.3 +/- 0.8 h. The AUC were identical: 682.3 +/- 126.2 (B) vs. 686.9 +/- 165.8 mg . h/l (V). After both preparations 67% of the given SMZ dose could be detected in urine within 48 h. In two out of the eight volunteers the absorption of B was delayed, but it passed off to the same extent. In all other cases absorption of the suspension was accelerated in comparison with tablet administration studies reported. Peak blood levels of TMP and SMZ after ingestion of the suspensions reach the lower range of values resulting from tablet intake. Both suspensions are regarded interchangeable with respect to bioavailability, which is also comparable to co-trimoxazole tablets.     

Pharmacokinetics and bioavailability of three dyphylline preparations

The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg X kg-1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16 +/- 0.18 h and for the tablet 2.59 +/- 0.56 h. The mean clearance rate for S was 13.6 +/- 1.7 h-1 and volume of distribution 43.0 +/- 3.91. Peak concentration (Cmax, micrograms X ml-1), time of peak (Tmax, h), area under the curve (AUC, micrograms X ml-1 X h) and relative bioavailability (RB, %), were determined for three preparations: Cmax S, 33.7 +/- 3.7; R, 27.7 +/- 4.2; SR, 10.4 +/- 1.5 Tmax: S, 0.33 +/- 0.0; R, 0.66 +/- 0.0; SR, 2.13 +/- 1.1 AUC: S, 108.4 +/- 12.1; R, 113.9 +/- 25.2; SR, 104.0 +/- 30.8 RB: Reference Product R, 105.00 +/- 16.00; SR, 100.00 +/- 25.00 The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg X kg-1 dose and establish bioequivalence for the products studied.