Authors: G L Amidon, H Lennernäs, V P Shah...

A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Biological Availability; Cimetidine; Gastric Emptying; In Vitro Techniques; Jejunum; Mathematics; Models, Theoretical; Permeability; Pharmaceutical Preparations; Piroxicam; Solubility

PubMed: 7617530
DOI: 10.1023/a:1016212804288

Review

Authors: Ida M Heerfordt, Catharina M Lerche, Hans Christian Wulf...

BACKGROUND

Erythropoietic protoporphyria (EPP) is caused by deficiency of the enzyme converting protoporphyrin IX (PpIX) into heme resulting in accumulation of PpIX; leading to photosensitivity and liver toxicity. Cimetidine might inhibit δ-aminolevulinic acid synthase influencing the heme biosynthesis. We present cases with EPP treated with cimetidine at our department, and a literature review.

METHODS

Systematic searches were performed to identify literature describing EPP patients treated with cimetidine. On that ground we treated EPP patients with cimetidine through spring and summer in 2020 and 2021 at our department. Their erythrocyte PpIX level and standard blood and liver parameters were collected before and during 4 months of treatment. Using a questionnaire, patients were asked about change in photosensitivity, side effects, and whether they would like to resume treatment in the spring of 2022.

RESULTS

Literature searches identified 9 patients treated with cimetidine. Four were outpatients reporting decreased photosensitivity. At our department 18 outpatients started treatment. Fifteen used oral cimetidine daily for 4 months or more providing a significant decrease in erythrocyte PpIX with a median of 20% (range: -18% to 53%) after 4 months. Eleven of the 15 patients reported a decrease in photosensitivity during treatment, 3 patients were unsure, and 1 patient experienced unchanged photosensitivity. Only mild side effects were reported. Fourteen patients requested to resume treatment in the spring of 2022.

CONCLUSIONS

These cases suggest that cimetidine can lower erythrocyte PpIX in patients with EPP.

Topics: Cimetidine; Ferrochelatase; Heme; Humans; Photochemotherapy; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins

PubMed: 35245673
DOI: 10.1016/j.pdpdt.2022.102793

Review

Authors: Steven King-Fan Loo, William Yuk-Ming Tang

INTRODUCTION

Warts are caused by the human papillomavirus (HPV), of which there are over 100 types, which probably infects the skin via areas of minimal trauma. Risk factors include use of communal showers, occupational handling of meat, and immunosuppression. In immunocompetent people, warts are harmless and resolve as a result of natural immunity within months or years.

METHODS AND OUTCOMES

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for warts (non-genital)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS

We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS

In this systematic, review we present information relating to the effectiveness and safety of the following interventions: intralesional bleomycin; cimetidine; contact immunotherapy; cryotherapy; duct tape occlusion; formaldehyde, glutaraldehyde; homeopathy; photodynamic treatment; pulsed dye laser; surgical procedures; topical salicylic acid; and zinc sulphate.

Topics: Administration, Oral; Bandages; Bleomycin; Cimetidine; Cryosurgery; Cryotherapy; Humans; Warts; Zinc Sulfate

PubMed: 21726478
DOI: No ID Found

Review

Authors:

Topics: Animals; Carcinogens; Cimetidine; Dogs; Female; Male; Mice; Molecular Structure; Pregnancy; Rats; Reproduction

PubMed: 2292801
DOI: No ID Found

Authors:

Topics: Chronic Disease; Cimetidine; Duodenal Ulcer; Guanidines; Humans; Time Factors

PubMed: 647322
DOI: 10.1136/bmj.1.6125.1435

Authors: A J Isaacs

Topics: Adult; Cimetidine; Guanidines; Humans; Male; Platelet Count; Sarcoidosis; Thrombocytopenia

PubMed: 7053219
DOI: 10.1136/bmj.280.6210.294

Authors: Omolbanin Oladpour, Fereshteh Taghipour, Zuhair Mohammad Hassan...

Cimetidine and ibuprofen exhibit immunomodulatory effects as an antagonist of histamine H2 receptor, and a cyclooxygenase inhibitor, respectively. Here, the effects of cimetidine and ibuprofen on some effector T cell-related parameters were investigated using a breast cancer (BC) model. BC was established in Balb/c mice using the 4T1 cell line. On day 10 after tumor induction, the BC-bearing mice were classified into four groups and treated with PBS, cimetidine (20 mg/kg), ibuprofen (20 mg/kg) or a combination of "cimetidine + ibuprofen" via intraperitoneal injection (daily from days 11 to 30). The mice were sacrificed on day 31 and the frequency of splenic Th1 and Treg cells, plasma IFN-γ and TGF-β levels, and intra-tumoral T-bet, GATA3, FOXP3 and RORγt expressions were detected using flowcytometry, ELISA and real-time-PCR, respectively. In untreated cancerous mice, the percentage of splenic Th1 cells and plasma IFN-γ levels were lower (P<0.003 and P<0.01, respectively), whereas the percentage of splenic Treg cells and plasma TGF-β levels were higher than in healthy mice (P<0.04 and P<0.005, respectively). Treatment of BC-bearing mice with cimetidine, ibuprofen or both drugs promoted the frequency of Th1 cells (P<0.05, P<0.007 and P<0.005, respectively) as well as IFN-γ levels (P<0.004, P<0.0001 and P<0.03, respectively), while reduced the frequencies of Treg cells (P<0.02, P<0.03 and P<0.01, respectively), TGF-β levels (P<0.006, P<0.02 and P<0.002, respectively), intra-tumoral expression of FOXP3 (P<0.006, P<0.005 and P<0.005, respectively), and intra-tumoral expression of RORγt (P<0.04, P<0.03 and P<0.05, respectively) compared with untreated BC mice. The "cimetidine + ibuprofen"-treated mice displayed greater T-bet expression than the un-treated mice (P<0.006). Cimetidine and/or ibuprofen-treated BC-bearing mice exhibited reduced intra-tumoral expression of GATA3 compared with the untreated BC mice, but the differences were not significant. Cimetidine and ibuprofen correct some effector T cell-related parameters in cancerous mice. Immunotherapeutic potentials cimetidine and ibuprofen in cancers need investigations.

Topics: Animals; Cimetidine; Disease Models, Animal; Forkhead Transcription Factors; Ibuprofen; Mice; Mice, Inbred BALB C; Neoplasms; Nuclear Receptor Subfamily 1, Group F, Member 3; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

PubMed: 35763623
DOI: 10.31557/APJCP.2022.23.6.1847

Authors: Mariane Castro Manzato, Fabiane de Santi, André Acácio Souza da Silva...

Submandibular gland (SMG) is responsive to androgens via androgen receptor (AR). We verified whether cimetidine induces androgenic dysfunction in SMG, and evaluated the structural integrity, cell death and immunoexpression of actin, EGF and V-ATPase in androgen-deficient SMG. Male rats received cimetidine (CMTG) and control animals (CG) received saline. Granular convoluted tubules (GCTs) diameter and number of acinar cell nuclei were evaluated. TUNEL and immunofluorescence reactions for detection of AR, testosterone, actin, EGF and V-ATPase were quantitatively analysed. In CG, testosterone immunolabelling was detected in acinar and ductal cells cytoplasm. AR-immunolabelled nuclei were observed in acinar cells whereas ductal cells showed AR-immunostained cytoplasm, indicating a non-genomic AR action. In CMTG, the weak testosterone and AR immunoexpression confirmed cimetidine-induced androgenic failure. A high cell death index was correlated with decreased number of acinar cells, GCTs diameter and EGF immunoexpression under androgenic dysfunction. Actin immunofluorescence decreased in the SMG cells, but an increased and diffuse cytoplasmic V-ATPase immunolabelling was observed in striated ducts, suggesting a disruption in the actin-dependent V-ATPase recycling due to androgenic failure. Our findings reinforce the androgenic role in the maintenance of SMG histophysiology, and point to a potential clinical use of cimetidine against androgen-dependent glandular tumour cells.

Topics: Actins; Animals; Cimetidine; Cytochrome P-450 CYP1A2 Inhibitors; Drug Evaluation, Preclinical; Epidermal Growth Factor; Male; Rats, Sprague-Dawley; Receptors, Androgen; Submandibular Gland; Testosterone; Vacuolar Proton-Translocating ATPases; Rats

PubMed: 33713423
DOI: 10.1111/joa.13408

Authors: M Mehta

Topics: Anti-Infective Agents; Cimetidine; Dapsone; Histamine H2 Antagonists; Humans; Methemoglobinemia; Postoperative Complications

PubMed: 17924910
DOI: 10.1111/j.1365-2044.2007.05332.x

Clinical Trial

Authors: P Mangtani, P Seed

Topics: Cimetidine; Humans; Obesity; Randomized Controlled Trials as Topic; Weight Loss

PubMed: 8518701
DOI: 10.1136/bmj.306.6891.1542-c