Bioavailability of morphine after administration of a new bioadhesive buccal tablet

A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration–time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the C_max of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found. © 1998 John Wiley & Sons, Ltd.     

Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation

Dihydroergotoxine mesylate (DHETM, CAS 8067-24-1), the combination of the mesylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocornine, dihydroergocristine, alpha-dihydroergocryptine and beta-dihydroergocryptine), is used mainly for age-related cognitive impairment. The bioavailability of DHETM was investigated in a cross-over study on 20 male healthy volunteers to whom two single doses of 9 mg DHETM were administered either in tablets (Orphol spezial) or in oral solution (Orphol forte). DHETM was assayed in serum with a double radioimmunoassay method displaying a satisfactory cross-reactivity with the principal components of DHETM. After administration of tablets the peak of DHETM was (mean +/- SE) 124 +/- 16 pg/ml, the tmax 1.15 +/- 0.21 h, the AUC 790 +/- 93 pg/ml x h and the terminal elimination half-life 7.54 +/- 1.23 h. After oral solution the peak of DHETM was 176 +/- 16 pg/ml, the tmax 0.50 +/- 0.04 h, the AUC 779 +/- 94 pg/ml x h and the terminal elimination half-life 6.13 +/- 0.76 h. The bioavailability of DHETM from tablets vs. that from oral solution differed only by a retard related to the dissolution time of DHETM from the tablets, but not for other pharmacokinetic parameters. The relatively high two single doses of 9 mg DHETM administered to the 20 subjects were well tolerated, causing only known and expected adverse reactions to DHETM (tiredness, headache and vertigo) that did not require discontinuation of the study.     

Bioavailability of a new ketoprofen formulation for once-daily oral administration

A new sustained-release formulation (sustained release Ibifen) that gradually releases ketoprofen within 24 h and ensures therapeutic plasma concentration for the entire period has been developed. It consists of tableted pH-dependent barrier film-coated ketoprofen granules and was administered at a single dose of 200 mg to 12 volunteers. Ketoprofen plasma profiles were compared with: (1) administration of Orudis retard 200 capsule (200 mg); (2) two 12-h doses of prompt release Ibifen capsules (100 mg). In vitro dissolution kinetics and ketoprofen plasma levels were measured by HPLC. Sustained release Ibifen dissolution rate was constant for 10 h, whereas Orudis retard 200 dissolution profile presented one higher slope (0-6 h) and a lower one (6-12 h). Both formulations showed a delayed kinetics with respect to prompt release Ibifen. After sustained release Ibifen administration, ketoprofen plasma peak, reached within 2 h, remained practically constant for at least 12 h (average 4 microg/ml), which is higher than therapeutic levels. Differently, Orudis retard 200 produced a delayed, higher C(max) (5.91+/-0.66 vs. 4.51+/-0.65 microg/ml; P<0.01) and disappeared more quickly. In conclusion, sustained release Ibifen can ensure therapeutic ketoprofen plasma levels for the entire 24 h period, avoiding plasma concentration spikes, with bioavailability similar to other ketoprofen preparations.     

Development of a prolonged-release gastroretentive tablet formulation of ciprofloxacin hydrochloride: pharmacokinetic characterization in healthy human volunteers

The fluroquinolone anti-biotic ciprofloxacin is primarily dissolved and absorbed from the upper part of the GI tract. We, therefore, aimed to develop a prolonged release gastroretentive (GT) formulation of ciprofloxacin that could be administered once daily with a conventional tablet (CT). A variety of polymers and effervescent properties were utilized to optimize the desired disposition profile. Tablets were prepared by the direct compression technique and evaluated for physical properties, swelling, floating, and drug release. In vivo studies were also carried out on the optimized GT formulation and CT in healthy volunteers. A very sensitive and reliable HPLC method was developed to measure plasma concentration of ciprofloxacin. The duration of floating times were predominantly >24 h and floating lag times <20 s. The drug release mechanism followed zero order kinetics. C(max), T(max), and AUC(0-∞) of GT vs CT were 0.945±0.29 vs 2.1±0.46 μg/ml, 6.0±1.42 vs 1.42±0.59 h and 8.54±1.87 vs 9.45±2.12 μg/ml/h, respectively. Pharmacokinetic parameters indicate that the developed GT formulation extended the pharmacokinetic profile achieved with CT. The C(max)/MIC and AUC(0-∞)/MIC, which are indicative of eradication of pathogens, following co-administration of GT with CT were comparable to those of twice-daily administration of CT alone.     

Bioavailability of a small unilamellar low-clearance liposomal amikacin formulation after extravascular administration

Amikacin in small, low-clearance liposomes (MiKasome) has prolonged plasma and tissue residence and in vivo activity against extracellular infections, including Klebsiella pneumonia and Pseudomonas endocarditis. Small liposomes may cross endothelial barriers, and enter the systemic circulation after extravascular administration. We compared the systemic bioavailability (F) of low-clearance liposomal amikacin in rats following intravenous (i.v.), intraperitoneal (i.p.), intramuscular (i.m.) and subcutaneous (s.c.) injection (20 mg/kg) and intratracheal (i.t.) instillation (10 mg/kg). Drug-containing liposomes were extensively absorbed after i.p. (F = 87-146%) and i.t. (F = 64%) administration, with maximum amikacin plasma concentrations of 171 micrograms/ml at 9 h and 80 micrograms/ml at 18 h, respectively. Absorption was slower and less extensive following s.c. (plasma Tmax: 20.3 micrograms/ml at 48 h) and i.m. (plasma Tmax: 49.6 micrograms/ml at 19 h) injection, but a significant fraction (12-27%) of the liposomes was absorbed. The plasma AUCs of liposomal amikacin exceeded the AUC of conventional i.v. amikacin by at least 25-fold for all routes. Amikacin AUCs in regional lymph nodes exceeded plasma AUCs by 4-fold after s.c. and i.m. injection of liposomal amikacin. AUCs in tissues surrounding the injection sites were 20- and 191-fold higher than plasma AUCs after i.m. and s.c. injection, respectively. Thus, small low-clearance liposomes produced sustained levels of liposome-encapsulated amikacin in plasma, local tissues and lymph nodes after extravascular administration, suggesting applications in perioperative prophylaxis, pneumonias and intralesional therapy as well as sustained systemic delivery of encapsulated drugs.     

Simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation by liquid chromatography

A rapid and accurate liquid chromatographic method is described for the simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation. Chromatographic separation of the two drugs was achieved on a Diamonsil™ C₁₈ column (200 mm×4.6 mm, 5 μm). The mobile phase consisting of a mixture of acetonitrile, methanol and 0.5% ammonium acetate (39:11:50 (v/v), pH 5.5) was delivered at a flow rate of 1.0 ml/min. Detection was performed at 220 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 201.2–2012.0 μg/ml for roxithromycin and 42.7–427.0 μg/ml for ambroxol hydrochloride, respectively. Separation was complete in less than 10 min. The proposed method can be used for the quality control of formulation products.     

Bioavailability study of a new amoxicillin tablet designed for several modes of oral administration

A new tablet of amoxicillin (Flemoxin solutab) has been formulated with galenic properties which allow it to be taken as a tablet, either swallowed, chewed or sucked, or to be taken after dispersion in water. This study was undertaken to compare the bioavailability of the new tablet (swallowed as such, or after dispersion) with a commercially available amoxicillin capsule and, for purposes of internal reference, with a Flemoxin forte suspension. Each formulation was administered to 12 volunteers according to a repeated 4 X 4 latin square design. Statistical analysis revealed that the tablet and suspension formulations tested gave significantly higher maximum plasma levels, occurring significantly faster after intake, when compared to the capsule. Furthermore, the new tablet showed a statistically significantly greater area under the plasma concentration-time curve with a highly predictable absorption when compared to the capsule. The method of intake of the new tablet appeared to be of no relevance with respect to the observed bioavailability.     

Interchangeability of two 500 mg amoxicillin capsules with one 1000 mg amoxicillin tablet after a single oral administration

The aim of the study was to evaluate if two capsules (Amoxil^® capsules, 500 mg/capsule) and one tablet (Amoxicare^® tablets, 1000 mg/tablet) of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil^®) and the other one with the generic tablet Amoxicare^®, with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC_0-8, AUC_0-∞, C_max, T_max, K_e and T_1/2 were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. C_max and AUC_0-∞ were statistically analyzed using analysis of variance (ANOVA); no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of C_max and AUC_0-∞ fall within the FDA specified bioequivalent limits (80-125%) suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption.     

Bioavailability of a new effervescent tablet of diclofenac

OBJECTIVE: The bioavailability of a newly developed effervescent tablet containing 50 mg diclofenac Na (DIC-effervesc) was investigated and compared with an enteric-coated dragée (DIC-enteric). SUBJECTS AND METHOD: 24 healthy, male and informed volunteers (mean body weight 78.8 kg, mean age 31.9 years) received in a randomized cross-over design a single dose of 50 mg diclofenac as DIC-effervesc and DIC-enteric. A total of 19 blood samples were obtained before and up to 12 h after administration according to the different properties of the galenic formulation. Diclofenac was analyzed by a sensitive HPLC method with a lower limit of quantification of 20 ng/ml. The bioavailability was compared as ratios of the geometric means of AUC0-infinity and Cmax. RESULTS: DIC-effervesc shows no lag time, a tmax within 30 min and a double peak of Cmax in 15/24 subjects. The mean Cmax (arithm. mean +/- SD) for DIC-effervesc is 950+/-341 ng/ml (first Cmax) and for DIC-enteric 1364+/-335 ng/ml. The mean AUC0-infinity, (arithm. mean +/- SD) amounts to 1097+/-210 ng/ml x h for DIC-effervesc and 1262+/-220 ng/ml x h for DIC-enteric. Based on the point estimator and the 90% interval DIC-effervesc is bioequivalent in respect to amount absorbed (86.4%; 81.8 - 91.3%). DIC-effervesc was well tolerated. CONCLUSION: The new effervescent tablet of diclofenac Na shows a rapid absorption without lag time, the same amount of absorption and a slightly lower Cmax (caused by a double peak phenomenon) in comparison to the enteric-coated dragee. A rapid onset of therapeutic effect is postulated in acute pain disorders.     

盐酸伪麻黄碱缓释片的相对生物利用度和稳态药物动力学

目的研究盐酸伪麻黄碱(Pse)缓释片的相对生物利用度及稳态药物动力学.方法12名健康志愿者单剂量或多剂量口服Pse缓释片或普通片,用高效液相色谱法测定血药浓度.结果Pse缓释片的相对生物利用度为(100.3±7.496)%.多剂量口服Pse缓释片和普通片稳态药物动力学参数AUC(0→t)(5626±980.8)和(1393±211.0)ng*h/ml,cmin(110.0±26.37)和(115.3±24.61)ng/ml,cmax(394.1±56.79)和(427.9±96.09)ng/ml以及FI∶1.126±0.179和1.19±0.137.结论研制的Pse缓释片可缓释24h,并与口服60mg,q6h普通片生物等效.其主要药物动力学参数与国外文献报道的基本一致.     

Bioavailability of tramadol hydrochloride after administration via different routes in rats

Tramadol is a synthetic non‐opiate analgesic drug and effective for many kinds of chronic and acute pain. This study compared the bioavailability of tramadol after different administration routes in rats (oral, buccal and nasal). A simple HPLC analytical approach was used to determine the concentration of tramadol in plasma. The pharmacokinetic behavior and bioavailability of tramadol after administration via different routes in rats were investigated. Nasal and buccal administration of tramadol resulted in a fast increase followed by a rapid decrease in the plasma tramadol concentration. The C_max values following buccal and nasal administration were 6 times and 20 times higher than that of oral administration, respectively, (6827.85 ± 7970.87 ng/ml, 22191.84 ± 5364.86 ng/ml, vs 1127.03 ± 778.34 ng/ml). The relative bioavailabilities of the nasal‐ and buccal‐administered drug when compared with the oral route were 504.8% and 183.4%, respectively, which is much higher than that of oral administration. Nasal and buccal administration increased the bioavailability of tramadol, which may allow for a reduction in the dose of tramadol and a subsequent decrease in both side effects and toxicity. Therefore, this approach provides an effective choice for the delivery of tramadol, an analgesic drug. Copyright © 2014 John Wiley & Sons, Ltd.     

Bioavailability and tolerance of xanthinol nicotinate depot preparations. Comparison of a conventional 500 mg xanthinol nicotinate depot tablet with new 500 mg and 1 g depot tablets

Bioavailability (therapeutic blood levels) and tolerance of two 500-mg xanthinol nicotinate retard tablet forms and one 1-g xanthinol nicotinate retard tablet (Complamin special) were tested in 11 (12) healthy volunteers. Despite the fact that both 500-mg retard tablets had different in vitro release rates the blood levels in man were similar. These results suggest that in vitro release rates of tablets do not predict corresponding blood levels in man. The tablet with a lower release rate also showed a distinctly lower flush rate. In respect to bioavailability and tolerance the 1-g xanthinol nicotinate retard tablet was comparable with corresponding dosages of 500-mg retard tablets. The dosage given was 2 X 500 mg or 1 g xanthinol nicotinate t.i.d. over a period of 10 days each.     

Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation

OBJECTIVES: The present study was conducted to assess the effect of food on the bioavailability of fenofibric acid from a new tablet formulation containing fenofibrate nanoparticles. METHODS: In this 3-way crossover study, 45 subjects received in a random order one 145 mg fenofibrate tablet under high-fat fed (HFF), low-fat fed (LFF) or fasting (reference) conditions. Plasma concentrations of fenofibric acid were determined up to 120 hours post-dose. Comparisons were made between test (HFF and LFF) and reference conditions (fasting). RESULTS: Very close values of pharmacokinetic parameters were obtained following the three diffiferent regimens. The 90% confidence intervals (CI) for the ratio of geometric means of HIFF versus fasting condition were (1.018-1.088) for AUCinfinity, (1.020-1.090) for AUCt and (0.963-1.054) for Cmax with point estimate:s of 1.052, 1.054 and 1.007, respectively. The 90% CI for the geometric means of LFF versus fasting condition were (0.978-1.046) for AUGinfinity, (0.981-1.047) for AUCt and (0.964-1.055) for Cmax with point estimates of 1.012, 1.013 and 1.009, respectively. They all fall within the required limits for bioequivalence (0.80-1.25). A slightly prolonged tmax was observed following HFF conditions (4.3 +/- 1.9 hours, versus 3.6 +/- 1.2 hours and 2.3 +/- 0.7 hours under LFF and fasting conditions, respectively), without any effect on mean Cmax. CONCLUSION: The peak and overall exposures from the new 145 mg fenofibrate tablet were not affected by food. Therefore, this new fenofibrate tablet may be taken without regard to the timing of meals.     

A pharmacodynamic and pharmacokinetic comparison of pindolol 20 mg retard and a conventional tablet

Summary In 10 healthy volunteers the time course of cardiac beta-adrenoceptor blocking activity, plasma levels and cumulative urinary excretion of pindolol were compared during a 4-day course of pindolol 5 mg (Visken^®) t. d. s., and one tablet of pindolol 20 mg retard (Visken^® retard) once a day. After oral administration of the 20 mg retard tablet, plasma concentrations of pindolol higher than half the maximum value (1/2 Cp (t_max)) were maintained about 2.5 times as long as after administration of the conventional 5 mg tablet. This is evidence for an important and marked retardation of drug release. During treatment with pindolol 20 mg retard once daily, cardiac beta-adrenoceptor blockade, measured by the reduction in exercise-induced tachycardia and in the exercise-induced rise in systolic blood pressure, at almost all times throughout the 24 h period was at least as great as during treatment with pindolol 5 mg t. d. s. This suggests that patients successfully treated with pindolol 5 mg t. d. s. can be maintained with the same beta-adrenoceptor blockade by a single tablet of pindolol 20 mg retard once daily.     

盐酸克林霉素棕榈酸酯分散片在健康人体的药代动力学和生物等效性

目的研究单次口服盐酸克林霉素棕榈酸酯分散片后的药代动力学及其生物等效性。方法用开放、随机、自身交叉的给药方案,20名健康志愿者单次口服盐酸克林霉素棕榈酸酯被试制剂或参比制剂,微生物法测定血清中药物浓度,计算2制剂的药代动力学参数并进行生物等效性评价。结果被试制剂与标准参比制剂在人体内的吸收、分布、代谢行为相似,2者的AUC0-t分别为(10.28±1.75),(10.75±2.11)mg·h·L-1;tmax分别为(1.25±0.34),(1.21±0.38)h;Cmax分别为(2.24±0.43),(2.18±0.61)mg·L-1;t1/2Ke分别为(3.27±0.40),(3.11±0.38)h,被试制剂的相对生物利用度为(96.70±11.30)%,经方差分析和双单侧检验,无显著性差异(P<0.05)。结论2制剂为生物等效制剂。     

Gastroscopic and pharmacokinetic evaluation of a new pivmecillinam tablet

Summary Three different pivmecillinam preparations, a conventional 200 mg tablet (P tablet) and two new formulations containing respectively pivmecillinam 200 mg and 400 mg plus Avicel^? (microcrystalline cellulose) as a disintegrator (PA tablet), were compared in vitro and in a gastroscopic study in 8 healthy volunteers. Disintegration of the PA tablet was significantly more rapid both in vitro and in the stomach. Following disintegration, the content of the PA tablet was spread over a larger area of the gastric mucosa (1088 mm²) than was observed with the P tablets (408 mm²). Three of the 8 volunteers taking the P tablet developed hyperaemia, interstitial bleeding or erosions of the mucosa of the stomach. No such reactions were seen with the PA tablets. Serum concentrations of mecillinam following ingestion of pivmecillinam tablets were determined in three groups of subjects; fasting volunteers, both supine and ambulant, and in ambulant subjects who took the preparation with a light meal. There was a tendency for the new PA tablets to produce a higher peak serum level as well as greater bioavailability of mecillinam. Administration of the PA tablets with a meal significantly increased the peak serum level and total bioavailability of the drug. On the basis of our observations we recommend adoption of the new PA tablet, because of its quick passage through the oesophagus and its more rapid and complete disintegration in the stomach.     

新型恩替卡韦制剂的药代动力学研究

目的测定大鼠血浆中恩替卡韦含量的液相色谱-串联质谱(LC-MS/MS)生物分析方法学的建立和验证以及新型恩替卡韦新制剂的药物代谢动力学研究。方法建立了测定大鼠血浆中恩替卡韦含量的液相色谱-串联质谱生物分析方法,并对所建立生物分析方法进行了方法学验证;然后,采用验证过生物分析方法在健康雄性Wistar大鼠体内对新型恩替卡韦制剂和原研药博路定片进行了非禁食情况下药物代谢动力学对比研究。结果方法学验证实验结果表明所建立的生物分析方法学符合相关验证要求;新型恩替卡韦制剂和原研药博路定片的血浓时间线下面积(AUC)分别为(672.5±65.7)和(461.3±10.9)ng·h·m L~(-1),并且这两种制剂所对应的半衰期(t1/2)分别为(11.06±3.21)和(6.66±0.92)h。结论试验结果表明在非禁食情况下新型恩替卡韦片剂明显优于原研药博路定片,新型恩替卡韦制剂的生物利用度(AUC)比博路定片提高了46.1%,并且将半衰期(t1/2)延长了67.1%。这些数据表明与原研药博路定片不同的是食物没有降低新型恩替卡韦片的生物利用度,因此,新研发的新型恩替卡韦制剂提高了疗效,有效地克服了原研药博路定片的食物影响。     

Bioequivalence testing of a new tablet formulation of generic fluoxetine.

The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.     

盐酸度洛西汀肠溶片在健康人体内的药物代谢动力学研究

目的研究健康受试者口服盐酸度洛西汀肠溶片后的体内药物代谢动力学特征。方法 20名健康受试者,男女各半,单次和多次口服盐酸度洛西汀肠溶片,进行药动学实验;采用LC-MS/MS法测定血浆中盐酸度洛西汀浓度,DAS 2.0进行药动学模型拟合和参数计算,SPSS 17.0软件进行统计分析。结果盐酸度洛西汀肠溶片的体内药动学符合一室开放模型,低、中、高剂量单次给药的主要药动学参数:实测值计算的平均Cmax分别为13.85±7.37、29.86±13.87、44.47±21.80μg·L-1,Tmax分别为7.60±3.47、6.80±1.40、6.80±1.40 h,统计矩计算的平均t1/2分别为13.93±6.88、11.57±2.34、12.19±1.73 h,AUC0-t分别为268.15±204.6、531.02±385.13、843.53±634.50μg·L-1·h-1;连续给药的主要药动学参数Cmax、Cmin、Cav分别为47.37±23.59、19.47±10.55、33.09±17.11μg·L-1,Tmax、t1/2分别为6.57±1.59、13.90±2.80 h,AUC0-t为1.13±0.68 mg·L-1·h-1。结论 20～60 mg盐酸度洛西汀肠溶片呈线性动力学特点,主要药物代谢动力学参数无性别差异,多次给药后体内无明显蓄积作用。     

Dose-related pharmacokinetics after oral administration of a new formulation of erythromycin base.

1 Erythromycin concentrations in serum and urine were determined in 24 healthy male, fasting subjects after oral administration of 250, 500, or 1000 mg of erythromycin base (250 mg capsules containing enteric-coated pellets). The subjects also received a film-coated erythromycin stearate tablet (equivalent to 500 mg base). 2 The mean +/- s.d. maximal serum erythromycin concentrations were 1.9 +/- 0.8, 3.8 +/- 1.4, 6.5 +/- 2.9 and 2.9 +/- 1.7 mg/l for 250, 500, or 1000 mg base and 500 mg stearate, respectively. The serum peaks usually occurred after 2 h irrespective of dosage form given. 3 The mean +/- s.d. areas under the serum concentration v time curves (AUC0-infinity) were 4.5 +/- 1.7, 11.2 +/- 4.3, 27.2 +/- 10.6 and 7.5 +/- 3.4 mg l -1 . h after 250, 500, or 1000 mg base, and 500 mg stearate, respectively. 4 The urinary recoveries were 5.0, 6.7, 8.6% of the base doses given and 4.4% of the stearate dose given. 5 Dose-dependent excretion of erythromycin occurred. The increase in AUC was larger than multiples of the lowest base dose.