抗疟药咯萘啶在兔体内的药代动力学

本文报道抗疟药咯萘啶iv,im和ig给药后在兔体内的药代动力学。用NONLIN程序对血药—时间数据进行拟合。一次快速iv 6 mg/kg后的血药—时间过程符合线性三室开模型。药代动力学参数(±SD):t 1/2_β为59±10h;V_c2.418±0.287L/kg;V_d(ss),29±6 L/kg;总清除率Cl_T为0.442±0.131 L/kg·h。Im和ig给药后的动力学过程以线性二室开模型描述。im 6 mg/kg,吸收速率常数K_a为33.5±21.8 h^-1,t 1/2_β为52±8 h,吸收完全。Ig 30或60 mg/kg后的k_a为2.41±1.26 h^-1,t 1/2_β为55±5 h,吸收程度为34.6%。咯萘啶在血中呈不均一分布,im后1～96 h,球/浆浓度比为3～6。     

Pharmacokinetics and bioavailability of oral and intramuscular artemether

Objective: The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. Results: Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18–24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [C_max: 474 vs 540 ng · ml⁻¹; t _max: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 μg · h · ml⁻¹]. Geographic means of lag-time and absorption half-life (t _1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively. t _1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60). Received: 18 October 1996 / Accepted in revised form: 28 January 1997     

Bioavailability and disposition kinetics of HI-6 in Beagle dogs

The absorption and disposition kinetics of HI-6 were determined in Beagle dogs given single doses (25 mg kg^?1) of the drug by the intravenous, intramuscular, and oral routes. Concentrations of the oxime in plasma and urine were measured by HPLC. A twocompartment open model was used to describe the disposition curve following intravenous drug administration while a one-compartment open model with first-order absorption adequately described the data following intramuscular or oral administration of the dose. Extravascular distribution of HI-6 was limited (V_ss 203 ml kg^?1) and the drug was eliminated rapidly after intravenous administration (t_1/2 46.5 min, MAT 55.4 min). Systemic clearance was 3.68 ml min^?1 × kg. A major fraction of the dose (63.7 per cent) was excreted in urine over a 24-h collection period. Following intramuscular drug administration, the absorption half-life (t_1/2(a), 5.3 min), MAT (17.1 min), C_max (70.37 μg ml^?1) and t_max (15.9 min) indicate that the drug was rapidly absorbed. Systemic availability was 83.43 per cent after oral drug administration, absorption was preceded by a lag time (23.2 min). The t_1/2(a) (41.5 min), MAT (81.6 min), C_max (4.30 μg ml^?1) and T_max (90.6 min) indicate somewhat delayed absorption. Systemic availability (11.38 per cent) and the fraction of dose excreted unchanged in the urine (9.3 per cent) show that the drug was poorly absorbed. The apparent half-life (58.0 min) and MRT (137.6 min) following oral administration were significantly longer (p <0.05) than following intravenous or intramuscular administration suggesting that the rate of absorption from the gastrointestinal tract decreases the elimination rate of the drug. In conclusion, HI-6 has limited distribution within the body, is rapidly eliminated mainly by renal excretion unchanged in the urine, and the bioavailability (i.e. rate and extent of absorption) of the drug varies with the route of administration.     

The effect of haemodialysis on the pharmacokinetics of tenoxicam in patients with end-stage renal disease

Summary We have studied the pharmacokinetics of tenoxicam after single and multiple oral doses of 20 mg in five patients (2 men and 3 women) with end-stage renal disease undergoing haemodialysis.After a single dose, tenoxicam had a half-life (t_1/2) of 33 h, an apparent clearance (CL·f^–1) of 4.3 ml·min^–1, and an apparent volume of distribution (V_z·f^–1) of 11.8 l. The maximum tenoxicam concentration (C_max) was 4.3 mg·l^–1 at a median t_max of 1.7 h. There were no significant differences between the values calculated from the pre- or post-dialyser port plasma samples.Tenoxicam plasma concentrations measured during once daily dosing before and after haemodialysis showed that tenoxicam does not accumulate.Our findings suggest that dosage adjustment may not be required in patients with end-stage renal disease on haemodialysis taking tenoxicam.     

Bioavailability studies with ciglitazone in beagles II. Effect of propantheline bromide and metoclopramide HCL on bioavailability of a tablet

Bioavailability studies in fasted dogs with ciglitazone (CGZ), an oral hypoglycemic agent, suggested that an absorption window could contribute to the poor oral availability of CGZ. If so, propantheline bromide (PPB) could increase the residence time of CGZ at absorption sites and increase its bioavailability. Using this rationale, a Latin square study was conducted with CGZ in fasted dogs (n = 10) using treatments of a single 125mg tablet with and without 1.2 mg kg⁻¹ i.m. PPB. PPB was given in a single dose 1 h prior to administration of CGZ. Plasma concentrations of CGZ were assayed by HPLC. PPB significantly increased the AUC of CGZ by a ratio of 1.2 : 1 (p < 0.01). PPB also increased T_max from 2–8 h (p<0.001), and appeared to produce first order absorption of CGZ. In a separate CGZ study using fasted dogs (n = 10), a single 125mg tablet was administered with and without i.v. metoclopramide HCI (MCP). A 10mg dose of MCP was given 15 min prior to dosing with CGZ and repeated 1 h after dosing. MCP increases GI motility and was expected to decrease residence time of CGZ. MCP had no effect on T_max, but significantly decreased AUC by 8 per cent (p = 0.05). MCP also reduced C_max by 16 per cent (p = 0.06). Taken as a whole, these data suggest that the effect of meals to increase bioavailability of CGZ could be mediated at least in part, through an increase in GI residence time.     

Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch

Abstract

1. A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson’s disease. Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration.

2. A total of 18 minipigs were randomly divided into three groups (six animals for each group). A single dose of 1?mg rasagiline tablet was orally administrated to one group. Meanwhile, single dose of 1.25 and 2.5?mg (2 and 4?cm²) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively. The pharmacokinetic parameters such as plasma half-life (t_1/2), time to peak plasma-concentration (T_max), mean residence time (MRT), area under the curve (AUC_(0–t)) were significantly (p?<?0.05) different between transdermal and oral administrations.

3. The plasma half-life (t_1/2) of rasagiline (1.25?mg patch: 11.8?±?6.5?h, 2.5?mg patch: 12.5?±?4.7?h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1?mg tablet: 4.7?±?2.5?h). The dose-normalized relative bioavailability of rasagiline patch in minipig were 178.5% and 156.4%, respectively, for 1.25 and 2.5?mg patches compared with 1?mg rasagiline tablet. The prolonged t_1/2 and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.     

Pharmacokinetics and bioavailabilities of hymecromone in human volunteers

Specific and ultrasensitive reverse-phase HPLC assays of the choleretic and biliary antispasmodic hymecromone (down to 0.05 ng ml^?1) and its glucuronide, using fluorimetric detection, and sulfate metabolities using UV detection, were developed. Sodium salt solutions of 400 mg (over 3 min) and 800 mg (over 5 min) were infused i.v. into 6–8 normal human volunteers. The half-life of the major rate constant averaged 28 ± 2 min (SE). Subsequently, less than 0.8 per cent of the dose was eliminated with terminal halflives of 70–359 min. The apparent volume of distribution of hymecromone, referenced to the total plasma concentration, averaged 20.8 ± 1.41 (V_c, central compartment volume) and 36.4 ± 2.11 (V_ss steady state volume). Hymecromone's total body clearance averaged 1413 ± 89 ml min^?1. The pharmacokinetics of hymecromone were doseindependent. Only 0.3 ± 0.3 per cent unchanged hymecromone was renally excreted. Mostly dose-independent glucuronidated drug (93 ± 4 per cent of the dose) was excreted in the urine; a smaller amount was renally excreted as the sulfate (1.4 ± 0.3 per cent of the dose). The oral bioavailability estimated from the relative areas under the hymecromone plasma concentration—time curves following oral and i.v. administration of hymecromone to six volunteer subjects showed no dose-dependence and was 1.8 ± 0.6 per cent. However, an anomalous c. 200 per cent of the glucuronide produced by i.v. hymecromone was produced from orally administered hymecromone as determined from the ratio of the AUC values of glucuronide obtained after peroral and i.v. administration of the same dose of hymecromone to demonstrate a high first-pass effect and implicate renal glucuronidation.     

盐酸普萘洛尔缓释片与常释片的生物利用度比较研究

目的：通过双交叉试验证明盐酸普萘洛尔缓释片有缓释作用。方法：用HPLC方法,测定血清中普萘洛尔浓度,进行盐酸普萘洛尔缓释片与常释片的生物利用度比较及峰谷浓度波动研究。结果：12位健康男性受试者一次交叉口服缓释片和常释片(均为40 mg)后的C_max分别为62.4±23.3和95.9±12.6 ng.mL^-1,AUC分别为360.2±80.6和383.5±74.2 ng.h.mL^-1,缓释片相对于常释片的相对生物利用度为95%;12位受试者连续服缓释片和常释片后平均稳态浓度分别为42.2±12.2和32.7±7.1 ng.mL^-1,波动度(DF)分别为0.90±0.35和2.09±0.34。结论：两种制剂具生物等效性,且缓释片比常释片有峰谷浓度差异小、血药浓度波动幅度小的特点。     

The pharmacokinetics of fentiazac and its metabolite,p-hydroxyfentiazac,after twice-daily oral administration to male volunteers

1. The pharmacokinetics of the anti-inflammatory agent fentiazac and its principal plasma metabolite, p-hydroxyfentiazac, have been investigated after repeated oral administration of fentiazac to male volunteers. Each volunteer received 200 mg of fentiazac twice daily for 15 d.

2. Absorption was quite rapid, though some inter-subject variation in rates of absorption and bioavailability was observed. t_max values after the first dose ranged from 0.75.3 h while CP_max values were 1050-4880 ng/ml.

3. Elimination of fentiazac from plasma occurred rapidly in curvilinear fashion, so that concentrations were only 1% of their maximum value by 12 h after dosing.

4. Maximum concentrations of p-hydroxyfentiazac after a single dose of fentiazac were 25.6-79.4% of those of fentiazac and were achieved at similar times. The metabolite was more slowly eliminated; the mean concentration of p-hydroxyfentiazac 12 h after a single dose was still 8% of its maximal value.

5. On repeated administration, AUC_0.12h values for fentiazac and hydroxyfentiazac increased, as indicated by accumulation factors of 1.17 ± 0.11 and 1.30± 0.11 on days 8 and 15, respectively, for fentiazac and 1.72 ± 015 and 1.77 ± 010 for hydroxyfentiazac

There was no significant difference between days 8 and 15 in the extent of accumulation of either compound. Trough concentrations of fentiazac and hydroxyfentiazac on days 12 and 15 were similar to those on day 8. The clinical significance of these observations is discussed.     

Pharmacokinetic and pharmacodynamic studies following single and multiple doses of rolafagrel,a novel inhibitor of thromboxane synthase,in normal volunteers

The pharmacokinetics and pharmacodynamics of rolafagrel (FCE 22178), a novel thromboxane synthase inhibitor, were evaluated after single and multiple oral doses in eight healthy volunteers. After a single dose (400 mg), the drug was absorbed rapidly, peak plasma concentrations being attained within 2 h in all subjects. Elimination followed a biphasic course, with a rapid initial decline followed after 12–24 h by a late phase with a terminal half-life of about 10h. About 100% of the administered dose could be recovered in urine within 72 h, mostly in conjugated form. During multiple dosing (400 mg t.i.d. for 5 days), steady-state conditions were approached on day 2 and AUC values over a dosing interval were similar to those observed after a single dose (72.3 vs 76.3 μg·ml⁻¹·h). Pharmacokinetic parameters calculated after multiple doses were similar to those observed after a single dose (C_max: 20.1 vs 18.2 μg·ml⁻¹; t_max: 1.2 vs 1.1 h; terminal half-life: 10.9 vs 11.4 h; CL: 85.2 vs 70.4 ml·h⁻¹;V: 1.23 vs 1.241·kg⁻¹). Platelet generation of thromboxane B₂, the stable breakdown product of thromboxane A₂, was inhibited by 85% at a plasma rolafagrel concentration of about 4μg·ml⁻¹, and only a small increase in inhibition was observed at higher concentrations.     

Pharmacokinetics and tissue disposition of danofloxacin in sheep

The plasma pharmacokinetics of danofloxacin administered at 1.25 mg kg⁻¹ body weight by the intravenous and intramuscular routes were determined in sheep. Tissue distribution was also determined following administration by the intramuscular route at 1.25 mg kg⁻¹ body weight. Danofloxacin had a large volume of distribution at steady state (V_ss) of 2.76±0.16 h (mean±S.E.M.) L kg⁻¹, an elimination half-life (t_1/2β) of 3.35±0.23 h, and a body clearance (C1) of 0.63±0.04 L kg⁻¹ h⁻¹. Following intramuscular administration it achieved a maximum concentration (C_max) of 0.32±0.02 μg mL⁻¹ at 1.23±0.34 h (t_max) and had a mean residence time (MRT) of 5.45±0.19 h. Danofloxacin had an absolute bioavailability (F) of 95.71±4.41% and a mean absorption time (MAT) of 0.81±0.20 h following intramuscular administration. Mean plasma concentrations of >0.06 μg mL⁻¹ were maintained for more than 8 h following intravenous and intramuscular administration. Following intramuscular administration highest concentrations were measured in plasma (0.43±0.04 μg mL⁻¹), lung (1.51±0.18 μg g⁻¹), and interdigital skin (0.64±0.18 μg g⁻¹) at 1 h, duodenal contents (0.81±0.40 μg mL⁻¹), lymph nodes (4.61±0.35 μg g⁻¹), and brain (0.06±0.00 μg mL⁻¹) at 2 h, jejunal (10.50±4.31 μg mL⁻¹) and ileal (5.25±1.67 μg mL⁻¹) contents at 4 h, and colonic contents (8.94±0.65 μg mL⁻¹) at 8 h. © 1998 John Wiley & Sons, Ltd.     

The pharmacokinetics of intravenous,intramuscular, and subcutaneous nalbuphine in healthy subjects

Summary The pharmacokinetics of intravenously, intramuscularly, and subcutaneously administered nalbuphine were studied in three parallel groups of 12 healthy volunteers each. The subjects received single doses of 10 mg and 20 mg of nalbuphine separated by a one week washout period. Blood specimens were obtained up to 15 h after dosing for determination of nalbuphine.Mean plasma nalbuphine concentrations 5 min after intravenous administration of 10 or 20 mg were 39 and 73 ng/ml, respectively. The mean maximum plasma concentrations (C_max) after intramuscular or subcutaneous administration of nalbuphine 10 mg were 29 and 31 ng/ml, respectively. Mean C_max values after 20 mg doses were 60 and 56 ng/ml. Mean C_max occurred 30 to 40 min after nalbuphine administration. The mean elimination half-lives of parenterally administered nalbuphine ranged between 2.2 and 2.6 h, regardless of dose given or route administered. The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine. The mean volumes of distribution (V_ss) of the intravenously administered drug were 290 and 274 l and the mean systemic clearances were 1.6 and 1.5 l/min following administration of 10 and 20 mg doses, respectively.Intramuscular and subcutaneous nalbuphine appear to be interchangeable based on the similarities in C_max, mean times until maximum concentration, mean AUC data, and absolute bioavailabilities.     

Single-dose bioavailability of oral and intramuscular thiocolchicoside in healthy volunteers

A single dose of 8 mg of thiocolchicoside was administered to 12 healthy volunteers according to a Latin square design, either as tablets (reference), oral solution, or intramuscular injection. Serum thiocolchicoside concentrations showed an absorption phase followed by a biexponential decay with a terminal half-life (t_1/2β) of approximately 5 h, similar for the three formulations. The relative bioavailability of both oral formulations was approximately 25%, compared to the intramuscular formulation. There was a trend for the oral solution to have a slightly larger AUC and C_max, as well as a slightly shorter T_max, than the tablet formulation. However, the comparison of the two oral forms did not show statistically significant differences in the pharmacokinetic parameters C_max, T_max, and AUC, suggesting that the Coltramyl^® tablets have an adequate in vivo dissolution profile.     

Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean±S.D.) were characterized by a low systemic plasma clearance (131.8±36.2 mL min⁻¹) and a small steady-state volume of distribution (12.6±2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter after i.v. (approximately 2 h) versus oral (approximately 5–7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. C_max was approximately 25% lower, and a median delay of 1.25 h in time to C_max was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times. © 1998 John Wiley & Sons, Ltd.     

Pharmacokinetics of isoforskolin after administration via different routes in guinea pigs

1.?The objective of this study was to characterize the pharmacokinetics of isoforskolin after oral, intraperitoneal and intravenous administration, as well as to compare bioavailability.

2.?Isoforskolin was administered to guinea pigs at a dose of 2?mg/kg. Plasma concentrations were determined by high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MS/MS) method. The pharmacokinetic parameters were calculated by a noncompartmental method. A compartment model was also adopted to describe the pharmacokinetic profiles.

3.?The pharmacokinetic behavior of intravenously administered isoforskolin was characterized by rapid and extensive distribution (V_z?=?16.82?±?8.42?L/kg) followed by rapid elimination from the body (Cl?=?9.63?±?4.21?L/kg/h). After intraperitoneal administration, isoforskolin was absorbed rapidly (T_max?=?0.12?±?0.05?h). The pharmacokinetic profiles of isoforskolin were similar after intraperitoneal and intravenous administration, except for the concentrations at the initial sampling times. Isoforskolin was also absorbed rapidly following oral dosing; however, the concentration–time data were best fit to a one-compartment model, which was different from that observed after intravenous and intraperitoneal administration. Following intraperitoneal and oral administration, the absolute bioavailability of isoforskolin was 64.12% and 49.25%, respectively.

4.?Isoforskolin is a good candidate for oral administration because of its good oral bioavailability.     

Disposition of SK&F L-190144 in rats and monkeys after oral,intravenous or ocular administration

The objective of the study was to investigate the systemic disposition of ¹⁴C-SK&F L-190144 after single intravenous (10mg kg^?1) and oral (200 mg kg^?1) doses to rats and after single intravenous and ocular doses (0.33 mg kg^?1) to monkeys. After the intravenous dose, the blood concentration-time profile of ¹⁴C-SK&F L-190144 followed a rapid triexponential decline with half-lives of 2.5, 15, and 246 min in rats and 3, 19, and 2520 min in monkeys. The ¹⁴C-label in blood was mainly the parent compound. The terminal elimination half-life detected in rats using the urinary excretion rate-time data was 700 min. The total body clearance values were 17.6 ± 2.1 (mean ± SD, n = 6) and 1.11 ± 0.41 (n=4) mlmin^?1 kg^?1 for rats and monkeys, respectively. Both species had similar values of volume of distribution at the terminal phase, 4 to 6 l kg^?1, and similar excretion patterns, approximately 60 per cent and 30 per cent of the dose were excreted in the urine and feces, respectively. ¹⁴C-SK&F L-190144 was not absorbed orally in rats with the majority of the dose recovered in the feces. Following ocular administration to monkeys, the plasma drug concentrations peaked at 8 h post-dosing but did not reach a biexponential elimination phase until 18 h post-dosing, suggesting slow systemic absorption of drug from the ocular site. The monkeys excreted 42 per cent of the dose in urine and 50 per cent in feces after ocular administration. This increase in fecal excretion compared to the intravenous route of administration may have been due to the slow absorption by the ocular and nasal tissues altering the relative proportions of drug elimination via the renal and hepatic routes, or to a proportion of the dose passing into the gastrointestinal tract and exiting unabsorbed. Study results demonstrate similar excretion patterns and volume of distribution after intravenous administration in both species. The slow terminal elimination phase in monkeys was attributed to the low body clearance. The low oral bioavailability was possibly due to the poor partitioning behavior of the drug (logarithm of partition coefficient - 2.6). A significant fraction of the dose was absorbed in the body via the ocular route.     

The pharmacokinetics of chlorbutol in man

The pharmacokinetics of chlorbutol were studied after oral administration in 4 healthy subjects on two occasions. Following the rapid attainment of peak concentrations, plasma concentrations fell by approximately 50 per cent in 24 h. After the first dose of chlorbutol, the terminal elimination half-life was 10.3 ± 1.3 days (mean ± S.E.M), the volume of distribution was 233 ± 141 and the plasma clearance was 11.6 ± l.0 ml min ^?1. The binding to plasma proteins was 57 ± 3 per cent. In 3 of the 4 subjects, there was a small but significant decrease in the terminal half-life of chlorbutol after the second dose. The mean urinary recovery over 17 days in two of the subjects accounted for only 9.6 per cent of the dose, 7.4 per cent of the total as the glucuronide and sulphate conjugates and 2.2 per cent as unchanged chlorbutol. A significant factor in the elimination of chlorbutol may be its instability under physiological conditions. Its half-life in vitro is 37 days at pH7.4. The long terminal half-life of chlorbutol makes it unsuitable as a sedative drug because of the considerable accumulation which will occur when the drug is taken in multiple doses.     

Isosorbide 5-mononitrate pharmacokinetics in humans

When isosorbide 5-mononitrate was intravenously infused at a rate of 4 mg h ^?1 for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml^?1 ± 5 per cent C.V. at 2.5 h and a steady-state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half-life of 4.2 h ± 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min^?1 ± 18 per cent C.V. and the volume of distribution was 48.4 1 ± 16 per cent C. V. After equal oral doses of 10 mg, the peak plasma isosorbide 5-mononitrate concentration of 191 ng ml^?1 ±16 per cent C.V. was reached at 1.1 h ± 30 per cent C.V., and plasma levels declined with a terminal half-life of 4.9 h. The complete systemic availability of isosorbide 5-mononitrate indicated that pre-systemic elimination after the oral doses was negligible. A one-compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral doses. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5-mononitrate metabolite of 72 ng ml^?1 ± 27 per cent C. V. occurred at l.7h.41 per cent C.V. Approximately 50 per cent (range 22–68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5-mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volume of distribution of the mononitrates.     

Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method

Twenty-four young healthy volunteers received a single dose of metformin 500 mg (Glucophage®, Nordic Laboratories, Canada) in tablet form. Plasma concentrations were determined by HPLC in samples collected prior to and 0.33, 0.66, 1.33, 1.66, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 15, 18, 24, and 30 h after dosing. Mean (± SD) C_max was 682.1 (160.6) ng ml^?1 at a mean (± SD) t_max of 2.4 (0.93) h. Overall elimination was monoexponential with a mean (± SD) half-life of 3.16 (0.47) h. We conclude that metformin is rapidly absorbed from this formulation and is also rapidly eliminated. Extrapolation to steady state predicts that equilibrium will be reached within 24 h.     

Bioavailability of fluvoxamine given with and without food

The influence of concomitant food intake on plasma concentrations of the antidepressant drug fluvoxamine maleate was investigated in a two-way, crossover study design. Eight male and four female healthy, young volunteers received a single oral dose of fluvoxamine maleate (50 mg, tablet) on two occasions: after an overnight fast and immediately after a breakfast. Food did not affect maximum fluvoxamine plasma levels (C_max), or the time to reach C_max (t_max). The plasma AUC of fluvoxamine was on average 7 per cent lower in the fed than in the fasted state. It is concluded that the effect of food on the pharmacokinetics of fluvoxamine is negligible.