Iqbal Ramzan

The University of Sydney · Faculty of Pharmacy

Vaccination, despite being recognized as one of the most effective primary public health measures, is viewed as unsafe and unnecessary by an increasing number of individuals. Anxiety about vaccines and vaccination programs leading to vaccine hesitancy results from a complex mix of social and political influences, cultural and religious beliefs, the...

Aim To compare the efficacy and safety of rituximab biosimilars to reference rituximab in patients with cancer. Data Sources A systematic review and meta‐analysis was conducted in accordance with PRISMA guidelines. MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to 12 January 2022 to obtain all randomised control trial...

The COVID-19 pandemic has shaken the world since early 2020 and its health, social, economic, and societal negative impacts at the global scale have been catastrophic. Since the early days of the pandemic, development of safe and effective vaccines was judged to be the best possible tool to minimize the effects of this pandemic. Drastic public heal...

Prophylactic vaccines are crucial in modern healthcare and have been used successfully to combat bacterial and viral infectious diseases. Infections like polio and smallpox, which were dreaded historically, and which devastated the human race over many centuries, are now rare. Smallpox has been eradicated completely and polio is nearly eradicated b...

This is a comprehensive primer, study guide, and primary reference text for pharmacists, doctors, and other health practitioners that presents the relevant science, clinical, policy, and regulatory frameworks for biologic medicines. The contents are pitched at a level that is easily understandable and can be immediately applied in everyday practice...

The salient language of innovator biologics, biosimilars, and biobetters are introduced, which deals with specific issues in greater detail pitched at pharmacists, doctors, and patients. Significant differences exist between biologic medicines including innovator biologics, biosimilars, and biobetters compared with chemically synthesized or isolate...

This chapter examines the knowledge areas and competency standards required by pharmacists and graduating pharmacy students on all aspects of biologic medicines. Pharmacists have a key role in the education of different speciality prescribers since clinicians in the United States and Europe are cautious about biosimilar use and do not predominantly...

A comprehensive primer and reference, this book provides pharmacists and health practitioners the relevant science and policy concepts behind biologics, biosimilars, and biobetters from a practical and clinical perspective. Explains what pharmacists need to discuss the equivalence, efficacy, safety, and risks of biosimilars with physicians, health...

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As its use becomes more widespread, so too are concerns around their cytotoxicity. Cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formatio...

Introduction/Background Radical hysterectomy for cervical cancer may be performed using a minimally invasive approach or and open, abdominal surgical approach. A growing body of evidence provides conflicting evidence regarding survival outcomes between these two surgical approaches. This study contributes a retrospective review of 10 years of data...

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiolo...

The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limi...

Among classes of nanoparticles developed as drug carriers and theranostics, nanodiamond (ND) has been gaining an increasing attention owing to its biocompatibility, easy functionalisation and chemical stability. Although biocompatibility studies on nanodiamond produced by detonation technique have been explored extensively, NDs produced by laser as...

The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicato...

The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicato...

Extracts of the pepper plant kava (Piper methysticum) are effective in alleviating anxiety in clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s) of the pharmacologically active constituents, kavalactones have not been established. γ-Aminobutyric acid type A receptors (GABAARs) are assumed to be the in v...

Scanning probe microscopy has been widely used to obtain topographical information and to quantify nanostructural properties of different materials. Qualitative and quantitative imaging is of particular interest to study material-material interactions and map surface properties on a nanoscale (i.e. stiffness and viscoelastic properties). These data...

Kava has been widely used as a herbal medicine for alternative treatment of anxiety and insomnia. In Europe, kava has been used for the treatment of anxiety and nervous disorders such as stress and restlessness, and in the United States kava is used as a natural alternative to anti-anxiety drugs and sleeping remedies. The most important medical app...

Phytotherapy, or the use of herbal medicines to prevent or treat a disease, is a modality of complementary and alternative medicine (CAM), or traditional medicine. This chapter introduces topics and issues involved in preclinical and clinical disciplines in phytotherapy. Pharmacognosy, particularly correct identification and high quality of the her...

Covering fundamentals and new developments in phytotherapy, this book combines pharmaceutical sciences and chemistry with clinical issues. • Helps readers better understand phytotherapy and learn the fundamentals of and how to analyze phytotherapeutic agents • Discusses phytotherapy in modern medicine, chemoprevention of disease, and alternatives t...

Metabolic pathways for kavalactone metabolism in humans and rats have been identified, but more detailed description of the enzyme kinetics involved is lacking. The disposition profiles of three of the six major kavalactones (kavain, methysticin and desmethoxyyangonin) and their respective metabolites (p-hydroxykavain, m,p-dihydroxykavain and p-hyd...

Previous studies with kava components such as kavalactones, pipermethystine and flavokavain B have demonstrated hepatotoxicity from these constituents. Regardless, there has recently been speculation that adulterants or impurities such as the mould hepatotoxin aflatoxin are a more likely cause of kava hepatotoxicity, despite a paucity of supporting...

The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender diff...

Liver toxicity is a side effect observed with some herbal treatments, including Piper methysticum. The possible mechanisms responsible include inflammation subsequent to activation of liver macrophages and oxidative damage. Hepatotoxicity of the pharmacologically active component of Piper methysticum (kavalactones) was tested in isolated, perfused...

Kakadu plum (Terminalia ferdinandiana Exell, Combretaceae) and Illawarra plum (Podocarpus elatus Endl., Podocarpaceae) extracts were fractionated, using a bioassay-guided approach and screened for antioxidant activity [oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays] and antiinflammatory activity (nitrite co...

The isolated perfused rat liver (IPRL) is a technique used in a wide range of liver studies. Typically livers are assessed at treatment end point. Techniques have been described to biopsy liver in the live rat and post-hepatectomy. This paper describes a technique for obtaining two full and one partial lobe biopsies from the liver in situ during an...

Four native Australian fruits, Illawarra Plum (Podocarpus elatus Endl., Podocarpaceae), Kakadu Plum (Terminalia ferdinandiana Exell, Combretaceae), Muntries (Kunzea pomifera F. Muell., Myrtaceae) and Native Currant (Acrotriche depressa R.Br., Epacridaceae) were examined for antioxidant and cellular protective activities. Each fruit showed significa...

Purified polyphenolic-rich extracts from four native Australian fruits, Illawarra Plum (Podocarpus elatus Endl., Podocarpaceae), Kakadu Plum (Terminalia ferdinandiana Exell, Combretaceae), Muntries (Kunzea pomifera F. Muell., Myrtaceae) and Native Currant (Acrotriche depressa R.Br., Epacridaceae), were screened for their ability to modulate anti-in...

Interest in dietary phytochemicals for potential cancer chemoprevention has increased substantially. Screening dietary compounds for chemopreventive activity however, requires a systematic and wide-ranging approach to encompass the complexity of carcinogenesis. We present some of the molecular pathways that underpin the broad biological processes i...

The pathophysiology of kava hepatotoxicity remains inconclusive. There is circumstantial evidence for the roles of toxic metabolites, inhibition of cyclooxygenase (COX) enzymes and depletion of liver glutathione. Pharmacogenomic effects are likely, particularly for Cytochrome P450 genes. Experimental and clinical cases of hepatotoxicity show eviden...

Apoptosis is one of the most critical forms of defense against cancer, and the induction of apoptosis by dietary polyphenols represents significant potential for cancer preventive activity. The present study examined polyphenols extracted from selected native Australian fruits--Illawarra plum (Podocarpus elatus Endl., Podocarpaceae), Kakadu plum (T...

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a chronic, mild f...

Investigation into phytochemicals from foods for disease prevention has increased substantially in the last few decades. However, a clear strategy on the selection of the most promising foods for research has been lacking. An ethnobotanical approach represents an effective method which may improve the outcomes of phytochemical research. Research on...

Dose form alteration, such as tablet crushing and splitting or capsule opening, is increasingly common in the age care setting. These practices are often used to facilitate enteral drug administration to patients with swallowing difficulties. Careful attention to issues, such as formulation characteristics, drug stability, medicine palatability and...

To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP and CLZ oxidation. Inhibition of CLZ oxidation...

The phenotyping cocktail is a practical approach for phenotyping of cytochrome P450 (CYP) enzymes in vivo. In this study, a liquid chromatography-tandem mass spectrometry method using a dual-extraction approach was developed and validated to quantify 5 selective substrates and their metabolites for the simultaneous phenotyping CYPs 1A2, 2C19, 2C9,...

Interest by prescribers and pharmacists in the provision of individualised pharmaceutical therapy in the form of compounded medicines has grown in recent times. However, there have also been a number of case reports of patient harm associated with these medicines. To highlight areas for clinicians and pharmacists to consider when prescribing or dis...

Three novel, simple and reproducible high-performance liquid chromatography quantitative assays with UV detection were developed and validated for three major kavalactones--desmethoxyyangonin, methysticin and kavain--in rat liver microsomes using diazepam as an internal standard; liquid-liquid extraction was used for sample preparation and analysis...

A sensitive, rapid LC-MS/MS assay has been developed and validated for the simultaneous quantification of CPT-11 and its two principal metabolites, 7-ethyl-10-hydroxycamptothecin (SN-38), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxy-camptothecin (APC) in human liver microsomal fractions and plasma. The method was linear over...

The atypical antipsychotic drug clozapine (CLZ) is effective in a substantial number of patients who exhibit treatment-resistance to conventional agents. CYP1A2 is generally considered to be the major enzyme involved in the biotransformation of CLZ to its N-demethylated (norCLZ) and N-oxygenated (CLZ N-oxide) metabolites in liver, but several studi...

To investigate whether the major kavalactone kavain imposes adverse effects on the liver ultrastructure and function by affecting vascular and microvascular architecture and altering hepatocellular morphology. Kavain solution (10 microg/mL or 43.5 micromol/L) was perfused for 2 h in isolated rat livers. After standard fixation and tissue preparatio...

Hepatic lipid infiltration (steatosis) is a complication of the metabolic syndrome and can progress to nonalcoholic steatohepatitis and severe liver injury. Microsomal cytochrome P450 (P450) drug oxidases are down-regulated in experimental steatosis. In this study we evaluated the separate and combined effects of lipid accumulation and P450 down-re...

In Australia, generic products must be bioequivalent to the innovator brand name product, or the market leader, before they are approved. Australia has rigorous scientifically-based evaluation procedures for generic medicines based on the internationally accepted principle of bioequivalence. Under the Pharmaceutical Benefits Scheme, generic substit...

Food and its constituents may have a significant effect on both the rate and extent of absorption of drugs after oral administration. Understanding the effect of meals on medicines enables health professionals to advise patients about taking medicines with or without food. Co-administration of drugs with food generally delays drug absorption. Howev...

The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perfusate reservoir, at doses of 10...

Kava kava, a beverage or extract prepared from the rhizome of the kava plant (Piper methysticum Forst. f.), was used for many centuries as a traditional beverage in the Pacific Islands. During the past few decades, kava has also gained popularity in Western countries as well, due to its anxiolytic and sedative properties. However, in recent years,...

In recent years, kava kava ( Piper methysticum, Forst. f., Piperaceae) has been implicated in a number of liver failure cases. Ever since this has kept the scientific world busy. Even though, on closer inspection, the majority of the case reports are probably not connected to kava intake, hepatotoxic effects of kava cannot generally be ruled out. I...

The hepatic disposition and biliary excretion of amphotericin B were investigated in the isolated perfused rat liver (IPRL). Bolus dose of 50 microg, 99 microg and 198 microg amphotericin B in lipoprotein-free perfusate and 198 microg amphotericin B in perfusate with 1 microM high-density lipoprotein (HDL) or 1 microM low-density lipoprotein (LDL)...

To develop a rapid online test of graft liver function during liver transplantation. Prospective, observational study. University hospital transplant unit. 17 adult patients with end-stage liver disease who underwent liver transplantation surgery. Rocuronium infusion dose requirements and plasma concentrations to maintain constant levels of neuromu...

Measurement of drug concentrations in target tissue has the potential to provide insight into the pharmacokinetics and pharmacodynamics of a drug. In this study, the distribution of the neuromuscular blocker, gallamine, into muscle tissue was investigated in urethane-anesthetized rats after an intravenous bolus dose (6 mg/kg). Microdialysis samplin...

A rapid, sensitive and selective method has been developed for the quantification of plasma concentrations of neuromuscular blocking drug, rocuronium, using gas chromatography with mass spectrometric detection. 3-Desacetylvecuronium served as the internal standard. The method involved iodide ion pair formation and a single-step liquid-liquid extrac...

Potential for assessing liver function during liver transplantation surgery by monitoring muscle paralysis from nondepolarizing neuromuscular blockers that are hepatically cleared is critically assessed. Rocuronium is strongly favored as a promising pharmacodynamic probe for predicting allograft liver function because it is predominantly eliminated...

Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentra...

We examined the effect of proton pump inhibitor omeprazole on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintaine...

The effect of histamine 2-antagonist famotidine on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs was examined in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintai...

Previous literature indicates possible interrelationships between the endogenous opioids or endorphins, pain response, and obesity or eating behaviour. The pain response was, therefore, examined in a rat model of obesity induced by palatable food high in unsaturated fats. Pellet-fed control and energy-dense obese and nonobese rats were tested for l...

The effect of ranitidine on gallamine-induced depression of twitch tension was evaluated in urethane-anaesthetized and mechanically ventilated male Sprague-Dawley rats. Gallamine was administered as an intravenous (IV) bolus and constant rate infusion in 15 rats to maintain 89 +/- 7% (SE) depression of twitch tension induced by electrical stimulati...

The hypothesis that the histamine H2 receptor blocker ranitidine potentiates neuromuscular paralysis during anaesthesia was tested in vivo in urethane anaesthetised and mechanically ventilated rats. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 48.5% (+/- 2.5 SEM) tibialis anterior muscle paralysis in 14 rats. R...

1. The effect of cimetidine on gallamine-induced neuromuscular paralysis was evaluated in urethane-anaesthetized and mechanically ventilated rats. 2. Intravenous cimetidine (between 3.2 and 100 mg/kg) produced an immediate and sustained potentiation of gallamine-induced neuromuscular paralysis. 3. Intravenous calcium (0.35 mmol/kg) completely rever...

The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 1...

A procedure for the determination of laudanosine, the central nervous system active metabolite of the neuromuscular blocking drug atracurium, in serum, cerebrospinal fluid and brain is described. The method uses a readily available internal standard, ethavrine, and a single-step protein precipitation with acetonitrile followed by high-performance l...

Glycerol acute renal failure (ARF) was examined to see if it alters theophylline (Th) neurotoxicity in rats. Concentrations of Th in serum, cerebrospinal fluid and in brain at seizure onset were similar in control and ARF rats infused with Th. Thus, glycerol ARF fails to alter Th neurotoxicity, an effect similar to that noted previously with uranyl...

The relationship between phenytoin-induced ataxia and its concentration was characterized in rats who received i.v. infusions of the drug at either 0.52, 0.85 or 1.70 mg/min/rat until the onset of ataxia. Phenytoin dose to ataxia did not change with infusion rate but the total and unbound serum concentrations at onset of ataxia increased with incre...

The neuromuscular action of ranitidine, an H2-receptor antagonist, was investigated by determining its effect on atracurium-induced neuromuscular blockade in urethane-anesthetized and mechanically ventilated male Sprague-Dawley rats. An intravenous bolus and an infusion of atracurium were administered to produce a stable 93 +/- 5% (n = 11) neuromus...

1. The effects of papaverine, an adenosine uptake inhibitor, were tested against theophylline-induced seizures. 2. Rats were infused with a constant intravenous infusion of theophylline at 10.3 mg/min immediately following intraperitoneal pretreatment with either papaverine 35 mg/kg or saline vehicle. 3. Papaverine produced a potent proconvulsant e...

The purpose of this investigation was to determine the optimum sampling site for phenytoin concentration measurements in the context of pharmacodynamic studies of the anticonvulsant effect of phenytoin. Determination of drug concentrations in the serum, serum water, brain, and cerebrospinal fluid (CSF) of rats as a function of time after iv injecti...

The purpose of this investigation was to determine if the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (PTZ) are altered in renal dysfunction. Female rats subjected to bilateral ureteral ligation (with sham-operated controls) or injected with uranyl nitrate (with saline injected controls) were infused intravenously wit...

The liver alcohol dehydrogenase inhibitor, 4-methylpyrazole, has been tested for its ability to change the hypnotic concentrations of phenobarbitone (phenobarbital) in rats. Following a single dose of 1 mmol kg-1 i.v., administered 60 min before phenobarbitone, 4-methylpyrazole shortened the onset time and reduced the dose of phenobarbitone require...

The present study was designed to examine the effect of aging on the neurotoxicity of theophylline in rats. Rats at one, three and six months of age were infused with intravenous theophylline (as aminophylline) at 1.03, 5.1 and 6.8 mg/mn respectively until onset of maximal seizures when theophylline concentrations were determined in serum, brain an...

The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophy...

The purpose of this investigation was to determine whether the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (1) are altered in advanced pregnancy. Lewis rats that were 20 days pregnant and nonpregnant rats of the same age and strain received either a relatively fast or a relatively slow intravenous infusion of 1 until...

Kinetics of gallamine, a neuromuscular blocker, were investigated in 22 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 60 min before CPB, 11 patients received 480 mg gallamine IV; the other 11 patients received an initial dose of 240 mg IV, followed by another 240 mg through the pump priming fluid at the sta...

The pharmacodynamics of the neuromuscular blocking drug gallamine were investigated in 10 surgical patients using a constant-rate infusion regimen, and results are compared to those for d-tubocurarine (dTc). Gallamine effect (paralysis)-time data gathered during and following the infusion were fitted to a pharmacodynamic effect model, while paralys...

Pharmacokinetics and pharmacodynamics of gallamine were assessed in seven patients undergoing surgery for correction of total biliary obstruction. Results were compared to those obtained in a previous study of 17 patients without obstruction. A significant increase in the steady-state volume of distribution of gallamine was noted in patients with b...

Local biotransformation enzymes and transporter proteins in tissues may exert a profound effect on drug pharma- cokinetics in those tissues. Thus, the use of drugs for the treatment of benign prostatic hyperplasia (BPH) and can- cer of the prostrate may be influenced by high level ex- pression of cytochrome P450 (CYP) phase I and phase II conjugati...

Hepatic lipid infiltration (steatosis) is an early lesion that may progress to non-alcoholic steatohepatitis and more severe liver disease. Drug metabolism is impaired in steatosis, which is due in part to decreased expression and function of cytochromes P450 (CYPs). The present study tested the impact of lipid deposition on microsomal CYP activity...